U.S. patent number 7,608,563 [Application Number 10/487,013] was granted by the patent office on 2009-10-27 for 3-phenoxy-4-pyridazinol derivatives and herbicide composition containing the same.
This patent grant is currently assigned to Mitsui Agro Chemicals, Inc.. Invention is credited to Junji Kadotani, Kiyoshi Koi, Hiroyuki Komai, Shigeru Mio, Hideo Takeshiba, Yoshihisa Tsukamoto.
United States Patent |
7,608,563 |
Tsukamoto , et al. |
October 27, 2009 |
**Please see images for:
( Certificate of Correction ) ** |
3-phenoxy-4-pyridazinol derivatives and herbicide composition
containing the same
Abstract
A compound represented by the formula: ##STR00001## [wherein
R.sup.1 represents a hydrogen atom, a halogen, atom, alkyl group,
etc., R.sup.2 represents a hydrogen atom, a halogen atom, alkyl
group, etc., R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each
independently represent a hydrogen atom, a halogen atom, a
substitutable alkyl group, a substitutable alkenyl group, alkynyl
group, a substituteable cycloalkyl group, etc., or R.sup.3,
R.sup.4, R.sup.5, R.sup.6 and R.sup.7 may form a ring which may be
substituted, which is formed by the adjacent two of them with
carbon atoms to which the respective substituents are bonded, m and
n each independently represent 0 or 1.] a salt thereof, an ester
derivative thereof and an agricultural chemical containing the same
as an effective ingredient, and a herbicidal composition containing
the compound and a second herbicidally active compound as effective
ingredients.
Inventors: |
Tsukamoto; Yoshihisa (Shiga,
JP), Komai; Hiroyuki (Shiga, JP), Kadotani;
Junji (Shiga, JP), Koi; Kiyoshi (Shiga,
JP), Mio; Shigeru (Shiga, JP), Takeshiba;
Hideo (Tokyo, JP) |
Assignee: |
Mitsui Agro Chemicals, Inc.
(Tokyo, JP)
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Family
ID: |
26620621 |
Appl.
No.: |
10/487,013 |
Filed: |
August 14, 2002 |
PCT
Filed: |
August 14, 2002 |
PCT No.: |
PCT/JP02/08278 |
371(c)(1),(2),(4) Date: |
February 27, 2004 |
PCT
Pub. No.: |
WO03/016286 |
PCT
Pub. Date: |
February 27, 2003 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20050037925 A1 |
Feb 17, 2005 |
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Foreign Application Priority Data
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Aug 17, 2001 [JP] |
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2001-248014 |
Mar 25, 2002 [JP] |
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2002-082219 |
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Current U.S.
Class: |
504/225; 544/240;
544/238; 544/114; 504/238 |
Current CPC
Class: |
C07D
403/12 (20130101); C07D 409/12 (20130101); C07D
405/12 (20130101); C07D 417/12 (20130101); C07D
401/12 (20130101); C07D 237/16 (20130101); C07D
413/12 (20130101); A01N 43/58 (20130101); A01N
43/58 (20130101); A01N 43/80 (20130101); A01N
43/56 (20130101); A01N 41/10 (20130101); A01N
43/58 (20130101); A01N 2300/00 (20130101) |
Current International
Class: |
A01N
43/84 (20060101); C07D 237/16 (20060101); C07D
403/02 (20060101); C07D 413/02 (20060101); A01N
43/58 (20060101) |
Field of
Search: |
;504/116,225,238
;514/252 ;544/239,240,114,238 |
References Cited
[Referenced By]
U.S. Patent Documents
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|
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4661486 |
April 1987 |
Takeshiba et al. |
5559080 |
September 1996 |
South et al. |
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Foreign Patent Documents
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0 470 856 |
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Feb 1992 |
|
EP |
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63-264575 |
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Nov 1988 |
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JP |
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Other References
Teruomi Jojima et al., "Pyridazines I. Novel Intramolecular
Cycloaddition of 3-Chloro-6- (2-allylphenoxy)pyridazines", Chem.
Pharm. Bull., 1972, vol. 20, No. 10, pp. 2191-2203. cited by other
.
Donald E. Ames et al., "[1,4]Benzodioxinopyridazines", Journal of
the Chemical Society: Perkin Transaction I, 1975, No. 6, pp.
534-538. cited by other .
The Pesticide Manual, 11th Edition, C.D.S. Tomlin, editor, pp. 111
to 112, pp. 1049 to 1050, and pp. 1054 to 1055 (1997). cited by
other .
The Pesticide Manual, 12th Edition, C.D.S. Tomln, editor, pp.
563-564, pp. 642-644 and pp. 848-849 (2000). cited by other .
P.M. Harrington et al, "Synthesis and Herbicidal Activity of
Cyperin", Journal of Agricultural and Food Chemistry, vol. 43, No.
3, pp. 804-808 (1995). cited by other.
|
Primary Examiner: Saeed; Kamal A
Assistant Examiner: Bianchi; Kristin
Attorney, Agent or Firm: Frishauf, Holtz, Goodman &
Chick, P.C.
Claims
The invention claimed is:
1. A compound represented by the formula: ##STR00034## wherein
R.sup.1 is a chlorine atom or a bromine atom, R.sup.2 is a hydrogen
atom, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each
independently represent a hydrogen atom, a fluorine atom, a
chlorine atom, a bromine atom, an iodine atom, a C.sub.1 to C.sub.4
alkyl group, a C.sub.3 to C.sub.4 cycloalkyl group, a cyano group,
a C.sub.2 to C.sub.3 alkoxycarbonyl group, a nitro group, a C.sub.1
to C.sub.3 alkoxy group or a trifluoromethoxy group, or R.sup.3,
R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are a group represented by
--CH.sub.2CH.sub.2CH.sub.2--, --CH(CH.sub.3)CH.sub.2CH.sub.2--,
OCH.sub.2CH.sub.2, --OCH.dbd.CH-- or ##STR00035## which is formed
by two adjacent members of R.sup.3, R.sup.4, R.sup.5, R.sup.6 and
R.sup.7, provided that R.sup.3 is not a hydrogen atom, and m and n
are both zero, a salt thereof or an ester thereof.
2. The compound, a salt thereof or an ester thereof according to
claim 1, wherein R.sup.1 is a chlorine atom.
3. The compound, a salt thereof or an ester thereof according to
claim 1, wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7
each independently represent a hydrogen atom, a fluorine atom, a
chlorine atom, a bromine atom, an iodine atom, a C.sub.1 to C.sub.3
alkyl group, a C.sub.3 to C.sub.4 cycloalkyl group, a cyano group
or a C.sub.1 to C.sub.2 alkoxy group, or R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 are a group represented by
--CH.sub.2CH.sub.2CH.sub.2-- or --OCH.dbd.CH--, which is formed by
two adjacent members of R.sup.3, R.sup.4, R.sup.5, R.sup.6 and
R.sup.7, provided that R.sup.3 is not a hydrogen atom.
4. The compound, a salt thereof or an ester thereof according to
claim 1, wherein R.sup.1 is a chlorine atom, R.sup.3, R.sup.4,
R.sup.5, R.sup.6 and R.sup.7 each independently represent a
hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an
iodine atom, a methyl group, an ethyl group, an isopropyl group, a
cyclopropyl group or a methoxy group, or R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 are a group represented by
--CH.sub.2CH.sub.2CH.sub.2--, which is formed by two adjacent
members of R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7, provided
that R.sup.3 is not a hydrogen atom.
5. The compound according to claim 1, wherein the compound is
selected from the group consisting of
6-chloro-3-(2-iodophenoxy)-4-pyridazinol,
6-chloro-3-(2-methyiphenoxy)-4-pyridazinol,
6-chloro-3-(2-cyclopropyiphenoxy)-4-pyridazinol,
6-chloro-3-(2,3-dihydro-1H-inden-4-yloxy)-4-pyridazinol,
3-(1-benzofuran-7-yloxy)-6-chloro-4-pyridazinol,
6-chloro-3-(2-methoxy-5-methylphenoxy)-4-pyridazinol,
6-chloro-3-(2-chloro-6-cyclopropylphenoxy)-4-pyridazinol,
3-(2-bromo-6-methylphenoxy)-6-chloro-4-pyridazinol,
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol and
6-chloro-3-(2-cyclopropyl-3,5-dimethyiphenoxy)-4-pyridaziflol, or a
salt thereof or an ester thereof.
6. The ester of the compound according to claims 1, 2, 3, 4 or 5,
in which a group bonded to the oxygen atom of the hydroxyl group at
the 4-position of the pyrazine ring is a C.sub.2 to C.sub.4
alkylcarbonyl group; a benzoyl group which is unsubstituted or
substituted with a methyl group or a
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yloxycarbonyl
group; a 1-azetidinylcarbonyl group; a 4-morpholinylcarbonyl group;
a C.sub.2 to C.sub.3 alkoxycarbonyl group which is unsubstituted or
substituted with 1 to 3 chlorine atoms; a dimethylcarbamoyl group;
a methoxy(methyl)carbamoyl group; a C.sub.1 to C.sub.3
alkylsulfonyl group which is unsubstituted or substituted with 1 to
3 fluorine atoms; or a phenylsulfonyl group which is unsubstituted
or substituted with a chlorine atom, a methyl group, a
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yloxysulfonyl
group or a nitro group.
7. The compound or a salt thereof or an ester thereof according to
claim 1, wherein the compound is
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methylbenzoate.
8. The compound or a salt thereof or an ester thereof according to
claim 1, wherein the compound is
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
dimethylcarbamate.
9. The compound or a salt thereof or an ester thereof according to
claim 1, wherein the compound is
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-propanesulfonate.
10. The compound or a salt thereof or an ester thereof according to
claim 1, wherein the compound is
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate.
11. The compound or a salt thereof or an ester thereof according to
claim 1, wherein the compound is
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-morpholinecarboxylate.
12. The compound or a salt thereof or an ester thereof according to
claim 1, wherein the compound is
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-azetizinecarboxylate.
13. The compound or a salt thereof or an ester thereof according to
claim 1, wherein the compound is
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
benzenesulfonate.
14. An agricultural chemical composition which comprises the
compound, a salt thereof or an ester thereof according to claim 1
as an effective ingredient in combination with a carrier.
15. A herbicidal composition which comprises (i) a herbicidally
effective amount of at least one 3-phenoxy-4-pyridazinol compound
selected from the group consisting of the compound, a salt thereof
or an ester thereof according to claim 1, and (ii) a herbicidally
effective amount of at least one herbicidally active compound
selected from the group consisting of
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-5-pyrazolyl-p-toluenesulfonate,
2-[4-(2,4-dichlorobenzoyl)-1,3-dimethylpyrazol-5-yloxy]acetophenone,
2-[4-(2,4-dichloro-m-toluoyl)-1,3-dimethylpyrazol-5-yloxy]-4'-methylaceto-
phenone, 5-cyclopropyl-1,2-oxazol-4-yl
.alpha.-.alpha.-.alpha.-trifluoro-2-mesyl-p-tolyl ketone,
2-(2-chloro-4-mesylbenzoyl)cyclohexan-1,3-dione,
2-(4-mesyl-2-nitrobenzoyl)cyclohexan-1,3-dione and
4-chloro-2-(methylsulfonyl)phenyl 5-cyclopropyl-4-isoxazolyl
ketone.
16. The herbicidal composition according to claim 15, wherein the
herbicidally active compound is
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-5-pyrazolyl-p-toluenesulfonate.
17. A method for killing weeds comprising applying to weeds or a
locus thereof a herbicidally effective amount of the compound, a
salt thereof or an ester according to claim 1.
18. A method for killing weeds comprising applying to weeds or a
locus thereof a herbicidally effective amount of the composition
according to claim 15.
Description
This application is the United States national phase application of
International Application PCT/JP02/08278 filed Aug. 14, 2002.
TECHNICAL FIELD
The present invention relates to a 3-phenoxy-4-pyridazinol
compound, its salt, its ester derivative and agricultural chemical
containing the same as an effective ingredient, and a herbicidal
composition containing 3-phenoxy-4-pyridazinol compound and a
second herbicidally active compound as effective ingredients.
BACKGROUND ART
In Chemical Pharmaceutical Bulletin, 1972, vol. 20, No. 10, pp.
2191-2203, 3-(2-allylphenoxy)-6-chloro-4-methoxypyridazine has been
disclosed but a 3-phenoxy-4-pyridazinol compound having a hydroxyl
group at the 4-position of the pyridazine has not been disclosed,
and there is no description about a herbicide.
In Journal of the Chemical Society: Perkin Transaction I, 1975, No.
6, pp. 534-538, 3-(2-hydroxyphenoxy)-4-methoxypyridazine and
6-chloro-3-(2-hydroxyphenoxy)-4-methoxypyridazine has been
disclosed but a 3-phenoxy-4-pyridazinol compound having a hydroxyl
group at the 4-position of the pyridazine has not been disclosed,
and there is no description about a herbicide.
In U.S. Pat. No. 5,559,080, a 3-(phenoxy which may be
substituted)pyridazine compound having a haloalkylphenoxy group at
the 4-position of the pyridazine has been disclosed but a
3-phenoxy-4-pyridazinol compound having a hydroxyl group at the
4-position of the pyridazine has not been disclosed. Also, in the
3-(phenoxy which may be substituted)pyridazine compound having a
haloalkylphenoxy group at the 4-position of the pyridazine, an
oxygen atom bonded to the 4-position of the pyridazine is bonded by
a benzene ring, and its herbicidal activity was insufficient.
Also, at present, a number of herbicides have been practically used
as a herbicide for a paddy field, and widely been used for general
purpose as a single agent and a mixed agent. However, there are
many kinds of paddy field weeds, and germination and growth period
of the respective weeds are not uniform, in particular, occurrence
of perennial weeds ranges for a long period of time. Thus, it is
extremely difficult to prevent from and kill all weeds with one
time spread of a herbicide. Accordingly, as a herbicide, an
appearance of a chemical which can kill many kinds of weeds
including annual weeds and perennial weeds, that is, which has a
wide weed-killing spectrum, is effective for already grown weeds,
preventing and killing effects of weeds of which can be maintained
for a certain period of time, and has high safety to paddy rice has
earnestly been desired.
Also, as upland herbicides, a number of herbicides have now been
commercially available and practically used, but there are many
kinds of weeds to be prevented, and occurrence thereof ranges for a
long period of time, so that a herbicide which has higher
herbicidal effects, has broad weed-killing spectrum, and causes no
chemical damage to crops has been desired.
One of the effective ingredient of the herbicidal composition of
the present invention (hereinafter referred to as a second
herbicidally active compound),
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-5-pyrazolyl-p-toluenesulfonate
[hereinafter referred to as Compound A. General name: Pyrazolate],
2-[4-(2,4-dichlorobenzoyl)-1,3-dimethylpyrazol-5-yloxy]acetophenone
[hereinafter referred to as Compound B. General name: Pyrazoxyfen],
2-[4-(2,4-dichloro-m-toluoyl)-1,3-dimethylpyrazol-5-yloxy]-4'-methylaceto-
phenone [hereinafter referred to as Compound C. General name:
Benzofenap], 5-cyclopropyl-1,2-oxazol-4-yl
.alpha.,.alpha.,.alpha.-trifluoro-2-mesyl-p-tolyl ketone
[hereinafter referred to as Compound D. General name:
Isoxaflutole], 2-(2-chloro-4-mesylbenzoyl)cyclohexan-1,3-dione
[hereinafter referred to as Compound E. General name: sulcotrione],
2-(4-mesyl-2-nitrobenzoyl)cyclohexan-1,3-dione [hereinafter
referred to as Compound F. General name: mesotrion] and
4-chloro-2-(methylsulfonyl)phenyl 5-cyclopropyl-4-isoxazolyl ketone
[hereinafter referred to as Compound G. General name:
Isoxachlortole] are each conventionally known herbicidal compound,
and each described in The Pesticide Manual 11th Edition, pp. 1049
to 1050, Ibid. pp. 1054 to 1055, Ibid. pp. 111 to 112, The
Pesticide Manual, 12th Edition p. 563, Ibid. p. 848, Ibid. p. 602
and EP 470 856(1990). These compounds have high effects against
annual broad-leaved weeds and a part of perennial weeds, but their
effects against rice plant weeds or a part of perennial weeds are
not necessarily sufficient.
DISCLOSURE OF THE INVENTION
The present inventors have earnestly studied about pyridazine
derivatives having a phenoxy group at the 3-position thereof, and
as a result, they have found that a compound having a hydroxyl
group at the 4-position of the pyridazine ring shows substantially
no chemical damage against paddy rice, and shows excellent
herbicidal activity against a wide range of weeds in a paddy field
with a low dosage to accomplish the present invention. Moreover,
they have found that similar herbicidal activities are possessed by
an ester derivative thereof in which a bonding between an oxygen
atom at the 4-position of the pyridazine ring and an acyl group is
cleaved in a soil or in a plant body to be converted into a
compound in which a hydrogen atom binds to the oxygen atom, whereby
accomplished the present invention.
Also, the present inventors have continued to search on a herbicide
which can completely prevent and remove various kinds of weeds with
one time spread, has extremely high safety to paddy rice or upland
crops, and has extremely low toxicity against humans and animals
for the purpose of overcoming the above-mentioned problems involved
in the conventional herbicides such as second herbicidally active
compounds A, B, C, D, E, F and G, and as a result, they have found
that by formulating the above-mentioned 3-phenoxy-4-pyridazinol
derivatives and the second herbicidally active compound as
effective ingredients, a weed-killing spectrum can be enlarged, and
serious weeds can be prevented and killed with a smaller amount of
effective ingredients by their synergistic action, whereby
accomplished the present invention.
The present invention relates to a compound represented by the
formula:
##STR00002## [wherein R.sup.1 represents a hydrogen atom, a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.6
haloalkyl group, a C.sub.3 to C.sub.6 cycloalkyl group, a C.sub.2
to C.sub.6 alkenyl group, a cyano group, a C.sub.2 to C.sub.7
alkylcarbonyl group, a di(C.sub.1 to C.sub.6 alkyl)carbamoyl group,
a phenyl group which may be substituted (The substituent is a
substituent selected from the following substituent Group A.), a 5
or 6-membered heterocyclic group (the heterocycle contains one
nitrogen atom, oxygen atom or sulfur atom in the ring, and may
contain further 1 or 2 nitrogen atom(s).), a C.sub.1 to C.sub.6
alkoxy group, a phenoxy group which may be substituted (The
substituent is a substituent selected from the following
substituent Group A.) or a 5- or 6-membered heterocycloxy group
which may be substituted {the heterocycle contains one nitrogen
atom, oxygen atom or sulfur atom in the ring, and may contain
further 1 or 2 nitrogen atom(s). The substituent is a
substituent(s) selected from the group consisting of a benzoyl
group which may be substituted (The substituent is a substituent
selected from the following substituent Group A.) and a C.sub.1 to
C.sub.6 alkyl group.},
R.sup.2 represents a hydrogen atom, a halogen atom, a C.sub.1 to
C.sub.6 alkyl group, a (C.sub.1 to C.sub.6 alkoxy)C.sub.1 to
C.sub.6 alkyl group, a benzoyl group which may be substituted (The
substituent is a substituent selected from the following
substituent Group A.), a C.sub.2 to C.sub.7 alkoxycarbonyl group, a
phenoxy group which may be substituted (The substituent is a
substituent selected from the following substituent Group A.), a
phenylthio group which may be substituted (The substituent is a
substituent selected from the following substituent Group A.) or a
tri(C.sub.1 to C.sub.6 alkyl)silyl group,
R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each independently
represent a hydrogen atom, a halogen atom, a C.sub.1 to C.sub.6
alkyl group which may be substituted (The substituent is a
substituent selected from the following substituent Group B.), a
C.sub.2 to C.sub.6 alkenyl group which may be substituted (The
substituent is a cyano group or a nitro group.), a C.sub.2 to
C.sub.6 alkynyl group, a C.sub.3 to C.sub.6 cycloalkyl group which
may be substituted (The substituent is a substituent selected from
the following substituent Group C.), a C.sub.4 to C.sub.10
bicycloalkyl group, a cyano group, a formyl group, a C.sub.2 to
C.sub.7 alkylcarbonyl group, a benzoyl group which may be
substituted (The substituent is a substituent selected from the
following substituent Group A.), a carboxyl group, a C.sub.2 to
C.sub.7 alkoxycarbonyl group, a carbamoyl group, a di(C.sub.1 to
C.sub.6 alkyl)-carbamoyl group, a phenyl group which may be
substituted (The substituent is a substituent selected from the
following substituent Group A.), a 3- to 6-membered heterocyclic
group which may be substituted (the heterocycle contains one
nitrogen atom, oxygen atom or sulfur atom in the ring, and may
contain further 1 or 2 nitrogen atom(s), or may be fused with a
benzene ring. The substituent is a substituent selected from the
following substituent Group E.), an amino group which may be
substituted (The substituent is a substituent selected from the
following substituent Group D.), a nitro group, a hydroxyl group, a
C.sub.1 to C.sub.6 alkoxy group, a C.sub.1 to C.sub.6 haloalkoxy
group, a (C.sub.1 to C.sub.6 alkoxy)C.sub.1 to C.sub.6 alkoxy
group, a phenoxy group which may be substituted (The substituent is
a hydroxyl group or a pyridazinyloxy group substituted by a
substituent(s) selected from the group consisting of a halogen atom
and a C.sub.1 to C.sub.6 alkoxy group.), a 5- to 6-membered
heterocycloxy group which may be substituted (the heterocycle
contains one nitrogen atom, oxygen atom or sulfur atom in the ring,
and may contain further 1 or 2 nitrogen atom(s). The substituent is
a substituent selected from the following substituent Group E.), a
phenylsulfonyloxy group which may be substituted (The substituent
is a substituent selected from the following substituent Group A.),
a C.sub.1 to C.sub.6 alkylthio group, a C.sub.1 to C.sub.6
alkylsulfinyl group, a C.sub.1 to C.sub.6 alkylsulfonyl group or a
tri(C.sub.1 to C.sub.6 alkyl)silyl group, or R.sup.3, R.sup.4,
R.sup.5, R.sup.6 and R.sup.7 may form a 3- to 6-membered cyclic
hydrocarbon group which may be substituted, which is formed by the
adjacent two of them with carbon atoms to which the respective
substituents are bonded (the cyclic hydrocarbon may be interrupted
by the same or different 1 to 2 hetero atom(s) selected from the
group consisting of a nitrogen atom, an oxygen atom and a sulfur
atom. The substituent is a halogen atom, a C.sub.1 to C.sub.6 alkyl
group, a hydroxy-C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to
C.sub.6 alkoxy group, an oxo group, a hydroxyimino group or a
C.sub.1 to C.sub.6 alkoxyimino group, and when the C.sub.1 to
C.sub.6 alkyl group is substituted, it may form another 3-membered
ring by combining, with the other C.sub.1 to C.sub.6 alkyl group or
a carbon atom(s) in the cyclic hydrocarbon.),
m and n each independently represent 0 or 1,
the substituent Group A is a group selected from the group
consisting of a halogen atom, a C.sub.1 to C.sub.6 alkyl group, a
C.sub.1 to C.sub.6 haloalkyl group, a C.sub.3 to C.sub.6 cycloalkyl
group, a cyano group and a tri(C.sub.1 to C.sub.6 alkyl)silyl
group,
the substituent Group B is a group selected from the group
consisting of a halogen atom, a C.sub.3 to C.sub.6 cycloalkyl
group, a cyano group, a C.sub.2 to C.sub.7 alkylcarbonyl group, a
C.sub.2 to C.sub.7 alkoxycarbonyl group, a phenyl group, a C.sub.1
to C.sub.6 alkoxy group, a C.sub.1 to C.sub.6 alkylthio group, a
C.sub.1 to C.sub.6 alkylsulfinyl group, a C.sub.1 to C.sub.6
alkylsulfonyl group, a C.sub.1 to C.sub.4 alkylenedioxy group, a
hydroxyimino group and a C.sub.1 to C.sub.6 alkoxyimino group,
the substituent Group C is a group selected from the group
consisting of a halogen atom, a C.sub.1 to C.sub.6 alkyl group
which may be substituted (The substituent is a substituent selected
from the above-mentioned substituent Group B.), a C.sub.3 to
C.sub.6 cycloalkyl group, a C.sub.2 to C.sub.6 alkenyl group, a
cyano group, a C.sub.2 to C.sub.7 alkylcarbonyl group, a benzoyl
group, a carboxyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group,
a carbamoyl group, a di(C.sub.1 to C.sub.6 alkyl)carbamoyl group, a
phenyl group which may be substituted (The substituent is a
substituent selected from the above-mentioned substituent Group
A.), a 5 or 6-membered heterocyclic group (the heterocycle contains
one nitrogen atom, oxygen atom or sulfur atom in the ring, and may
contain further 1 or 2 nitrogen atom(s).), an amino group which may
be substituted (The substituent is a substituent selected from the
following substituent Group D.), a nitro group, a hydroxyl group, a
C.sub.1 to C.sub.6 alkoxy group, a C.sub.1 to C.sub.6 haloalkoxy
group, a phenoxy group, a C.sub.1 to C.sub.6 alkylthio group, a
phenylthio group, a C.sub.1 to C.sub.6 alkylsulfinyl group and a
C.sub.1 to C.sub.6 alkylsulfonyl group,
the substituent Group D is a group selected from the group
consisting of a C.sub.1 to C.sub.6 alkyl group, a C.sub.2 to
C.sub.7 alkylcarbonyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl
group, a di(C.sub.1 to C.sub.6 alkyl)carbamoyl group and a C.sub.1
to C.sub.6 alkylsulfonyl group,
the substituent Group E is a group selected from the group
consisting of a halogen atom, a C.sub.1 to C.sub.6 alkyl group, a
C.sub.1 to C.sub.6 haloalkyl group, a hydroxyl group, a
phenylsulfonyl group which may be substituted (The substituent is a
substituent selected from the above-mentioned substituent Group A.)
and a di(C.sub.1 to C.sub.6 alkyl)sulfamoyl group.], its salt or
its ester derivative, an agricultural chemical containing the same
as an effective ingredient, and, a herbicidal composition
containing one or more 3-phenoxy-4-pyridazinol derivatives selected
from the group consisting of the above-mentioned compounds, their
salt and their ester derivatives, and one or more second
herbicidally active compound selected from the group consisting
of
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-5-pyrazolyl-p-toluenesulfonate,
2-[4-(2,4-dichlorobenzoyl)-1,3-dimethylpyrazol-5-yloxy]acetophenone,
2-[4-(2,4-dichloro-m-toluoyl)-1,3-dimethylpyrazol-5-yloxy]-4'-methylaceto-
phenone, 5-cyclopropyl-1,2-oxazol-4-yl
.alpha.,.alpha.,.alpha.-trifluoro-2-mesyl-p-tolyl ketone,
2-(2-chloro-4-mesylbenzoyl)cyclohexan-1,3-dione,
2-(4-mesyl-2-nitrobenzoyl)cyclohexan-1,3-dione and
4-chloro-2-(methylsulfonyl)phenyl 5-cyclopropyl-4-isoxazolyl ketone
as effective ingredients.
In the present invention, "a halogen atom" is a fluorine atom, a
chlorine atom, a bromine atom or an iodine atom, preferably a
fluorine atom, a chlorine atom or a bromine atom, more preferably a
chlorine atom or a bromine atom, still further preferably a
chlorine atom.
In the present invention, the "C.sub.1 to C.sub.6 alkyl group" is a
straight or branched alkyl group having 1 to 6 carbon atoms, for
example, it may be methyl, ethyl, propyl, isopropyl, butyl,
isobutyl, s-butyl, t-butyl, pentyl, isopentyl, 2-methylbutyl,
neopentyl, 1-ethylpropyl, hexyl, 4-methylpentyl, 3-methylpentyl,
2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl,
2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl,
1,3-dimethylbutyl, 2,3-dimethylbutyl or 2-ethylbutyl group,
preferably a straight or branched alkyl group having 1 to 4 carbon
atoms (a C.sub.1 to C.sub.4 alkyl group), more preferably a
straight or branched alkyl group having 1 to 3 carbon atoms (a
C.sub.1 to C.sub.3 alkyl group), still further preferably an alkyl
group having 1 to 2 carbon atoms (a C.sub.1 to C.sub.2 alkyl
group), particularly preferably a methyl group.
In the present invention, the "C.sub.1 to C.sub.6 haloalkyl group"
is the "C.sub.1 to C.sub.6 alkyl group" to which the same or
different above-mentioned 1 to 5 "a halogen atom(s)" is/are
substituted, and for example, it may be chloromethyl,
dichloromethyl, trichloromethyl, 1-chloroethyl, 2-chloroethyl,
2,2,2-trichloroethyl, 1-chloropropyl, 3-chloropropyl,
1-chlorobutyl, 4-chlorobutyl, fluoromethyl, difluoromethyl,
trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl,
2,2,2-trifluoroethyl, pentafluoroethyl, fluorochloromethyl,
bromomethyl, 1-bromoethyl, 2-bromoethyl or iodomethyl group,
preferably a C.sub.1 to C.sub.3 alkyl group substituted by the same
or different 1 to 3 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom and a bromine atom,
more preferably a C.sub.1 to C.sub.2 alkyl group substituted by the
same 1 to 3 fluorine atom(s) or chlorine atom(s), still further
preferably a fluoromethyl, difluoromethyl, trifluoromethyl or
2,2,2-trichloroethyl group, particularly preferably a
trifluoromethyl group.
In the present invention, the "C.sub.3 to C.sub.6 cycloalkyl group"
is a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group,
preferably cyclopropyl or cyclobutyl group, more preferably
cyclopropyl group.
In the present invention, the "C.sub.2 to C.sub.6 alkenyl group" is
a straight or branched alkenyl group having 2 to 6 carbon atoms,
for example, it may be vinyl, 1-methylvinyl, 1-propenyl,
1-methyl-1-propenyl, 2-propenyl, 1-methyl-2-propenyl,
2-methyl-2-propenyl, 2-ethyl-2-propenyl, 2-butenyl,
1-methyl-2-butenyl, 2-methyl-2-butenyl, 1-ethyl-2-butenyl,
3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl,
1-ethyl-3-butenyl, 2-pentenyl, 1-methyl-2-pentenyl,
2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl,
2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl,
2-methyl-4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl or 5-hexenyl
group, preferably a straight or branched alkenyl group having 2 to
4 carbon atoms (a C.sub.2 to C.sub.4 alkenyl group), more
preferably a vinyl, 1-methylvinyl, 2-propenyl or
1-methyl-2-propenyl group.
In the present invention, the "C.sub.2 to C.sub.7 alkylcarbonyl
group" is a carbonyl group to which the above-mentioned "C.sub.1 to
C.sub.6 alkyl group" is bonded, and for example, it may be an
acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl,
pivaloyl, hexanoyl or heptanoyl group, preferably a carbonyl group
to which a straight or branched alkyl group having 1 to 4 carbon
atoms is bonded (a C.sub.2 to C.sub.5 alkylcarbonyl group), still
further preferably a carbonyl group to which a straight or branched
alkyl group having 1 to 3 carbon atoms is bonded (a C.sub.2 to
C.sub.4 alkylcarbonyl group), particularly preferably an acetyl,
propionyl, valeryl or pivaloyl group, most preferably an acetyl
group.
In the present invention, the "di(C.sub.1 to C.sub.6
alkyl)-carbamoyl group" is a carbamoyl group in which the same or
different two above-mentioned "C.sub.1 to C.sub.6 alkyl groups" are
bonded to a nitrogen atom, and for example, it may be a
dimethylcarbamoyl, methylethylcarbamoyl, diethylcarbamoyl,
dipropylcarbamoyl, dibutylcarbamoyl or dihexylcarbamoyl group,
preferably a carbamoyl group in which the same two straight or
branched alkyl groups having 1 to 3 carbon atoms are bonded {a
di(C.sub.1 to C.sub.3 alkyl)carbamoyl group}, more preferably a
dimethylcarbamoyl group or a diethylcarbamoyl group, still further
preferably a dimethylcarbamoyl group.
In the present invention, the "tri(C.sub.1 to C.sub.6 alkyl)-silyl
group" is a silicon atom to which the same or different three
above-mentioned "C.sub.1 to C.sub.6 alkyl groups" are bonded, and
for example, it may be a trimethylsilyl, triethylsilyl,
triisopropylsilyl, dimethylisopropylsilyl, t-butyldimethylsilyl or
trihexylsilyl group, preferably a silicon atom to which the same or
different three straight or branched alkyl groups having 1 to 3
carbon atoms are bonded {a tri(C.sub.1 to C.sub.3 alkyl)silyl
group}, more preferably a trimethylsilyl or dimethylisopropylsilyl
group, still further preferably a trimethylsilyl group.
In the present invention, "a phenyl group which may be substituted
(The substituent is a substituent selected from the substituent
Group A.)" is a phenyl group which may be substituted by the same
or different 1 to 5 substituent(s) selected from the group
consisting of the above-mentioned "halogen atom", the
above-mentioned "C.sub.1 to C.sub.6 alkyl group", the
above-mentioned "C.sub.1 to C.sub.6 haloalkyl group", the
above-mentioned "C.sub.3 to C.sub.6 cycloalkyl group", a cyano
group and the above-mentioned "tri(C.sub.1 to C.sub.6 alkyl)-silyl
group", and for example, it may be a phenyl, fluorophenyl,
difluorophenyl, trifluorophenyl, chlorophenyl, dichlorophenyl,
trichlorophenyl, fluorochlorophenyl, methylphenyl, dimethylphenyl,
trimethylphenyl, tetramethylphenyl, pentamethylphenyl, ethylphenyl,
fluoro(methyl)phenyl, chloro(methyl)phenyl, bromo(methyl)phenyl,
cyclopropylphenyl, cyclopropyl(fluoro)phenyl,
chloro(cyclopropyl)phenyl, cyclopropyl(methyl)phenyl,
(trifluoromethyl)phenyl or fluoro(trifluoromethyl)phenyl group,
preferably a phenyl group which may be substituted by the same or
different 1 to 3 substituent(s) selected from the group consisting
of a fluorine atom, a chlorine atom, a bromine atom, a C.sub.1 to
C.sub.3 alkyl group, "a C.sub.1 to C.sub.3 alkyl group substituted
by the same or different 1 to 3 substituent(s) selected from the
group consisting of a fluorine atom, a chlorine atom and a bromine
atom", a C.sub.3 to C.sub.4 cycloalkyl group, a cyano group and a
tri(C.sub.1 to C.sub.3 alkyl)silyl group, more preferably a phenyl,
chlorophenyl, methylphenyl, trifluorophenyl or cyanophenyl
group.
In the present invention, the "5 or 6-membered heterocyclic group
(the heterocycle contains one nitrogen atom, oxygen atom or sulfur
atom in the ring, and may contain further 1 or 2 nitrogen
atom(s).)" is a 5- to 6-membered heterocyclic group which contains
one nitrogen atom, oxygen atom or sulfur atom as a hetero atom and
may further contain 1 to 2 nitrogen atom(s), and for example, it
may be a furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl,
isoxazolyl, oxazolyl, isothiazolyl, thiazolyl, triazolyl, pyranyl,
pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl or triazinyl group,
preferably a 5-membered heterocyclic group (the heterocycle
contains one nitrogen atom, oxygen atom or sulfur atom in the
ring.), more preferably a furyl or thienyl group.
In the present invention, the "C.sub.1 to C.sub.6 alkoxy group" is
a straight or branched alkoxy group having 1 to 6 carbon atoms, and
for example, it may be a methoxy, ethoxy, propoxy, isopropoxy,
butoxy, isobutoxy, s-butoxy, t-butoxy, pentoxy, isopentoxy,
2-methylbutoxy, neopentoxy, 1-ethylpropoxy, hexyloxy,
4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 1-methylpentoxy,
3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy,
1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,3-dimethylbutoxy or
2-ethylbutoxy group, preferably a straight or branched alkoxy group
having 1 to 3 carbon atoms (a C.sub.1 to C.sub.3 alkoxy group),
more preferably a methoxy or ethoxy group, still further preferably
a methoxy group.
In the present invention, the "phenoxy group which may be
substituted (The substituent is a substituent selected from the
substituent Group A.)" is a phenoxy group which may be substituted
by the same or different 1 to 5 substituent(s) selected from the
group consisting of the above-mentioned "halogen atom", the
above-mentioned "C.sub.1 to C.sub.6 alkyl group", the
above-mentioned "C.sub.1 to C.sub.6 haloalkyl group", the
above-mentioned "C.sub.3 to C.sub.6 cycloalkyl group", a cyano
group and the above-mentioned "tri(C.sub.1 to C.sub.6 alkyl)-silyl
group", and for example, it may be a phenoxy, fluorophenoxy,
difluorophenoxy, trifluorophenoxy, chlorophenoxy, dichlorophenoxy,
trichlorophenoxy, fluorochlorophenoxy, methylphenoxy,
dimethylphenoxy, trimethylphenoxy, tetramethylphenoxy,
pentamethylphenoxy, ethylphenoxy, fluoro(methyl)phenoxy,
chloro(methyl)phenoxy, bromo(methyl)phenoxy, cyclopropylphenoxy,
cyclopropyl(fluoro)phenoxy, chloro(cyclopropyl)phenoxy,
cyclopropyl(methyl)phenoxy, (trifluoromethyl)phenoxy or
fluoro(trifluoromethyl)phenoxy group, preferably a phenoxy group
which may be substituted by the same or different 1 to 3
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl
group, "a C.sub.1 to C.sub.3 alkyl group substituted by the same or
different 1 to 3 substituent(s) selected from the group consisting
of a fluorine atom, a chlorine atom and a bromine atom", a C.sub.3
to C.sub.4 cycloalkyl group, a cyano group and a tri(C.sub.1 to
C.sub.3 alkyl)silyl group, more preferably a phenoxy,
chlorophenoxy, methylphenoxy, trifluorophenoxy or cyanophenoxy
group.
In the present invention, "a benzoyl group which may be substituted
(The substituent is a substituent selected from the substituent
Group A.)" is a benzoyl group which may be substituted by the same
or different 1 to 5 substituent(s) selected from the group
consisting of the above-mentioned "halogen atom", the
above-mentioned "C.sub.1 to C.sub.6 alkyl group", the
above-mentioned "C.sub.1 to C.sub.6 haloalkyl group", the
above-mentioned "C.sub.3 to C.sub.6 cycloalkyl group", a cyano
group and the above-mentioned "tri(C.sub.1 to C.sub.6 alkyl)silyl
group", and for example, it may be a benzoyl, fluorobenzoyl,
difluorobenzoyl, trifluorobenzoyl, chlorobenzoyl, dichlorobenzoyl,
trichlorobenzoyl, fluorochlorobenzoyl, methylbenzoyl,
dimethylbenzoyl, trimethylbenzoyl, tetramethylbenzoyl,
pentamethylbenzoyl, ethylbenzoyl, fluoro(methyl)benzoyl,
chloro(methyl)benzoyl, bromo(methyl)benzoyl, cyclopropylbenzoyl,
cyclopropyl(fluoro)benzoyl, chloro(cyclopropyl)benzoyl,
cyclopropyl(methyl)benzoyl, (trifluoromethyl)benzoyl or
fluoro(trifluoromethyl)benzoyl group, preferably a benzoyl group
which may be substituted by the same or different 1 to 3
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl
group, "a C.sub.1 to C.sub.3 alkyl group which may be substituted
by the same or different 1 to 3 substituent(s) selected from the
group consisting of a fluorine atom, a chlorine atom and a bromine
atom", a C.sub.3 to C.sub.4 cycloalkyl group, a cyano group and a
tri(C.sub.1 to C.sub.3 alkyl)silyl group, more preferably a
benzoyl, chlorobenzoyl, dichlorobenzoyl, methylbenzoyl,
trifluorobenzoyl or cyanobenzoyl group.
In the present invention, "the 5- or 6-membered heterocycloxy group
which may be substituted {the heterocycle contains one nitrogen
atom, oxygen atom or sulfur atom in the ring, and may contain
further 1 or 2 nitrogen atom(s). The substituent may be substituted
by a substituent(s) selected from the group consisting of a benzoyl
group which may be substituted (The substituent is a substituent
selected from the substituent Group A.) and a C.sub.1 to C.sub.6
alkyl group.}" is "a 5- to 6-membered heterocycloxy group which
contains one nitrogen atom, oxygen atom or sulfur atom as a hetero
atom, and may contain further 1 or 2 nitrogen atom(s)" which may be
substituted by the same or different 1 to 3 substituent(s) selected
from the group consisting of the above-mentioned "a benzoyl group
which may be substituted (The substituent is a substituent selected
from the substituent Group A.)" and the above-mentioned "C.sub.1 to
C.sub.6 alkyl group", preferably a benzoyl group which may be
substituted by the same or different 1 to 3 substituent(s) selected
from the group consisting of a fluorine atom, a chlorine atom, a
bromine atom, a C.sub.1 to C.sub.3 alkyl group, "a C.sub.1 to
C.sub.3 alkyl group substituted by the same or different 1 to 3
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom and a bromine atom", a C.sub.3 to C.sub.4
cycloalkyl group, a cyano group and a tri(C.sub.1 to C.sub.3
alkyl)silyl group, and "a 5-membered heterocycloxy group which
contains one nitrogen atom, oxygen atom or sulfur atom as a hetero
atom, and which may contain further one nitrogen atom" substituted
by the same two C.sub.1 to C.sub.3 alkyl groups, more preferably a
benzoyl group substituted by two chlorine atoms and a pyrazolyloxy
group substituted by two C.sub.1 to C.sub.2 alkyl groups.
In the present invention, "the (C.sub.1 to C.sub.6 alkoxy)-C.sub.1
to C.sub.6 alkyl group" is the above-mentioned "C.sub.1 to C.sub.6
alkyl group" substituted by one of the above-mentioned "C.sub.1 to
C.sub.6 alkoxy groups", and for example, it may be a methoxymethyl,
ethoxymethyl, propoxymethyl, butoxymethyl, s-butoxymethyl,
t-butoxymethyl, pentyloxymethyl, hexyloxymethyl, methoxyethyl,
ethoxyethyl, propoxyethyl, butoxyethyl, methoxypropyl,
methoxybutyl, methoxypentyl or methoxyhexyl group, preferably a
C.sub.1 to C.sub.6 alkyl group substituted by one C.sub.1 to
C.sub.3 alkoxy group, more preferably a methoxyethyl, ethoxyethyl
or ethoxymethyl group.
In the present invention, "C.sub.2 to C.sub.7 alkoxycarbonyl group"
is a carbonyl group to which the above-mentioned "C.sub.1 to
C.sub.6 alkoxy group" is bonded, and for example, it may be a
methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,
isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,
s-butoxycarbonyl, t-butoxycarbonyl, pentoxycarbonyl,
isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl,
1-ethylpropoxycarbonyl, hexyloxycarbonyl, 4-methylpentoxycarbonyl,
3-methylpentoxycarbonyl, 2-methylpentoxycarbonyl,
1-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl,
2,2-dimethylbutoxycarbonyl, 1,1-dimethylbutoxycarbonyl,
1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl,
2,3-dimethylbutoxycarbonyl or 2-ethylbutoxycarbonyl group,
preferably a carbonyl group to which a C.sub.1 to C.sub.3 alkoxy
group is bonded (a C.sub.2 to C.sub.4 alkoxycarbonyl group), more
preferably a methoxycarbonyl or ethoxycarbonyl group, still further
preferably a methoxycarbonyl group.
In the present invention, "the phenylthio group which may be
substituted (The substituent is a substituent selected from the
substituent Group A.)" is a phenylthio group which may be
substituted by the same or different 1 to 5 substituent(s) selected
from the group consisting of the above-mentioned "halogen atom",
the above-mentioned "C.sub.1 to C.sub.6 alkyl group", the
above-mentioned "C.sub.1 to C.sub.6 haloalkyl group", the
above-mentioned "C.sub.3 to C.sub.6 cycloalkyl group", a cyano
group and the above-mentioned "tri(C.sub.1 to C.sub.6 alkyl)silyl
group", and for example, it may beta phenylthio, fluorophenylthio,
difluorophenylthio, trifluorophenylthio, chlorophenylthio,
dichlorophenylthio, trichlorophenylthio, fluorochlorophenylthio,
methylphenylthio, dimethylphenylthio, trimethylphenylthio,
tetramethylphenylthio, pentamethylphenylthio, ethylphenylthio,
fluoro(methyl)phenylthio, chloro(methyl)phenylthio,
bromo(methyl)phenylthio, cyclopropylphenylthio,
cyclopropyl(fluoro)phenylthio, chloro(cyclopropyl)phenylthio,
cyclopropyl(methyl)phenylthio, (trifluoromethyl)phenylthio or
fluoro(trifluoromethyl)phenylthio group, preferably a phenylthio
group which may be substituted by the same or different 1 to 3
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl
group, "a C.sub.1 to C.sub.3 alkyl group which is substituted by
the same or different 1 to 3 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom and a bromine atom",
a C.sub.3 to C.sub.4 cycloalkyl group, a cyano group and a
tri(C.sub.1 to C.sub.3 alkyl)silyl group, more preferably a
phenylthio, chlorophenylthio, methylphenylthio, trifluorophenylthio
or cyanophenylthio group.
In the present invention, "the C.sub.1 to C.sub.6 alkylthio group"
is a straight or branched alkylthio group having 1 to 6 carbon
atoms, and for example, it may be a methylthio, ethylthio,
propylthio, isopropylthio, butylthio, isobutylthio, s-butylthio,
t-butylthio, pentylthio, isopentylthio, 2-methylbutylthio,
neopentylthio, 1-ethylpropylthio, hexylthio, 4-methylpentylthio,
3-methylpentylthio, 2-methylpentylthio, 1-methylpentylthio,
3,3-dimethylbutylthio, 2,2-dimethylbutylthio,
1,1-dimethylbutylthio, 1,2-dimethylbutylthio,
1,3-dimethylbutylthio, 2,3-dimethylbutylthio or 2-ethylbutylthio
group, preferably a straight or branched alkylthio group having 1
to 3 carbon atoms (a C.sub.1 to C.sub.3 alkylthio group), more
preferably a methylthio or ethylthio group, still further
preferably a methylthio group.
In the present invention, "the C.sub.1 to C.sub.6 alkylsulfinyl
group" is a straight or branched alkylsulfinyl group having 1 to 6
carbon atoms, and for example, it may be a methylsulfinyl,
ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl,
isobutylsulfinyl, s-butylsulfinyl, t-butylsulfinyl, pentylsulfinyl,
isopentylsulfinyl, 2-methylbutylsulfinyl, neopentylsulfinyl,
1-ethylpropylsulfinyl, hexylsulfinyl, 4-methylpentylsulfinyl,
3-methylpentylsulfinyl, 2-methylpentylsulfinyl,
1-methylpentylsulfinyl, 3,3-dimethylbutylsulfinyl,
2,2-dimethylbutylsulfinyl, 1,1-dimethylbutylsulfinyl,
1,2-dimethylbutylsulfinyl, 1,3-dimethylbutylsulfinyl,
2,3-dimethylbutylsulfinyl or 2-ethylbutylsulfinyl group, preferably
a straight or branched alkylsulfinyl group having 1 to 3 carbon
atoms (a C.sub.1 to C.sub.3 alkylsulfinyl group), more preferably a
methylsulfinyl or ethylsulfinyl group, still further preferably a
methylsulfinyl group.
In the present invention, "the C.sub.1 to C.sub.6 alkylsulfonyl
group" is a straight or branched alkylsulfonyl group having 1 to 6
carbon atoms, and for example, it may be a methylsulfonyl,
ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl,
isobutylsulfonyl, s-butylsulfonyl, t-butylsulfonyl, pentylsulfonyl,
isopentylsulfonyl, 2-methylbutylsulfonyl, neopentylsulfonyl,
1-ethylpropylsulfonyl, hexylsulfonyl, 4-methylpentylsulfonyl,
3-methylpentylsulfonyl, 2-methylpentylsulfonyl,
1-methylpentylsulfonyl, 3,3-dimethylbutylsulfonyl,
2,2-dimethylbutylsulfonyl, 1,1-dimethylbutylsulfonyl,
1,2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl,
2,3-dimethylbutylsulfonyl or 2-ethylbutylsulfonyl group, preferably
a straight or branched alkylsulfonyl group having 1 to 3 carbon
atoms (a C.sub.1 to C.sub.3 alkylsulfonyl group), more preferably a
methylsulfonyl or ethylsulfonyl group, still further preferably a
methylsulfonyl group.
In the present invention, "the C.sub.1 to C.sub.4 alkylenedioxy
group" is a straight or branched alkylenedioxy group having 1 to 4
carbon atoms, and for example, it may be a methylenedioxy,
ethylenedioxy, propylenedioxy, trimethylenedioxy or
tetramethylenedioxy group, preferably an alkylenedioxy group having
1 to 2 carbon atoms, more preferably a 1,2-ethylenedioxy group.
In the present invention, "the C.sub.1 to C.sub.6 alkoxyimino
group" is a straight or branched alkoxyimino group having 1 to 6
carbon atoms, and for example, it may be a methoxyimino,
ethoxyimino, propoxyimino, isopropoxyimino, butoxyimino,
isobutoxyimino, s-butoxyimino, t-butoxyimino, pentoxyimino,
isopentoxyimino, 2-methylbutoxyimino, neopentoxyimino,
1-ethylpropoxyimino, hexyloxyimino, 4-methylpentoxyimino,
3-methylpentoxyimino, 2-methylpentoxyimino, 1-methylpentoxyimino,
3,3-dimethylbutoxyimino, 2,2-dimethylbutoxyimino,
1,1-dimethylbutoxyimino, 1,2-dimethylbutoxyimino,
1,3-dimethylbutoxyimino, 2,3-dimethylbutoxyimino or
2-ethylbutoxyimino group, preferably a straight or branched
alkoxyimino group having 1 to 3 carbon atoms (a C.sub.1 to C.sub.3
alkoxyimino group), more preferably a methoxyimino or ethoxyimino
group, still further preferably a methoxyimino group.
In the present invention, "the C.sub.1 to C.sub.6 alkyl group which
may be substituted (The substituent is a substituent selected from
the substituent Group B.)" is the above-mentioned "C.sub.1 to
C.sub.6 alkyl group" which may be substituted by the
above-mentioned "a halogen atom", or by the above-mentioned
"C.sub.3 to C.sub.6 cycloalkyl group", a cyano group, the
above-mentioned "C.sub.2 to C.sub.7 alkylcarbonyl group", the
above-mentioned "C.sub.2 to C.sub.7 alkoxycarbonyl group", a phenyl
group, the above-mentioned "C.sub.1 to C.sub.6 alkoxy group", the
above-mentioned "C.sub.1 to C.sub.6 alkylthio group", the
above-mentioned "C.sub.1 to C.sub.6 alkylsulfinyl group", the
above-mentioned "C.sub.1 to C.sub.6 alkylsulfonyl group", the
above-mentioned "C.sub.1 to C.sub.4 alkylenedioxy group", a
hydroxyimino group or the above-mentioned "C.sub.1 to C.sub.6
alkoxyimino group", and for example, it may be a fluoromethyl,
difluoromethyl, trifluoromethyl, 2,2,2-trichloroethyl,
cyclopropylmethyl, cyanomethyl, acetylmethyl, acetylethyl,
methoxycarbonylmethyl, methoxycarbonylethyl, ethoxycarbonylmethyl,
ethoxycarbonylethyl, benzyl, methoxmethyl, methoxyethyl,
ethoxymethyl, ethoxyethyl, methylthiomethyl, methylthioethyl,
ethylthiomethyl, ethylthioethyl, methylsulfinylmethyl,
methylsulfonylmethyl, 2-(1,3-dioxolanyl), hydroxyiminomethyl or
methoxyiminomethyl group, preferably a C.sub.1 to C.sub.3 alkyl
group substituted by the same or different 1 to 3 substituent(s)
selected from the group consisting of a fluorine atom, a chlorine
atom and a bromine atom, or a C.sub.1 to C.sub.3 alkyl group which
may be substituted by a C.sub.3 to C.sub.4 cycloalkyl group, a
cyano group, a C.sub.2 to C.sub.4 alkylcarbonyl group, a C.sub.2 to
C.sub.4 alkoxycarbonyl group, a phenyl group, a C.sub.1 to C.sub.3
alkoxy group, a C.sub.1 to C.sub.3 alkylthio group, a C.sub.1 to
C.sub.3 alkylsulfinyl group, a C.sub.1 to C.sub.3 alkylsulfonyl
group, a C.sub.1 to C.sub.2 alkylenedioxy group, a hydroxyimino
group or a C.sub.1 to C.sub.3 alkoxyimino group, more preferably a
C.sub.1 to C.sub.2 alkyl group substituted by the same 1 to 3
fluorine atom(s) or chlorine atom(s), or a C.sub.1 to C.sub.2 alkyl
group which may be substituted by a cyclopropyl group, a cyano
group, a C.sub.2 to C.sub.3 alkylcarbonyl group, a C.sub.2 to
C.sub.3 alkoxycarbonyl group, a phenyl group, a C.sub.1 to C.sub.2
alkoxy group, a C.sub.1 to C.sub.2 alkylthio group, a C.sub.1 to
C.sub.2 alkylsulfinyl group, a C.sub.1 to C.sub.2 alkylsulfonyl
group, an ethylenedioxy group, a hydroxyimino group or a C.sub.1 to
C.sub.2 alkoxyimino group.
In the present invention, "the substituted C.sub.2 to C.sub.6
alkenyl group (The substituent is a cyano group or a nitro group.)
" is the above-mentioned "C.sub.2 to C.sub.6 alkenyl group"
substituted by a cyano group or a nitro group, preferably a C.sub.2
to C.sub.3 alkenyl group substituted by a cyano group or a nitro
group, more preferably a cyanovinyl or nitrovinyl group.
In the present invention, "the C.sub.2 to C.sub.6 alkynyl group" is
a straight or branched alkynyl group having 2 to 6 carbon atoms,
and for example, it may be ethynyl, 2-propynyl,
1-methyl-2-propynyl, 1-ethyl-2-propynyl, 2-butynyl,
1-methyl-2-butynyl, 1-ethyl-2-butynyl, 3-butynyl,
1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butynyl,
2-pentynyl, 1-methyl-2-pentynyl, 1-ethyl-2-pentynyl, 3-pentynyl,
1-methyl-3-pentynyl, 2-methyl-3-pentynyl, 4-pentynyl,
1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 2-hexynyl, 3-hexynyl,
4-hexynyl or 5-hexynyl, preferably a straight or branched alkynyl
group having 3 to 4 carbon atoms (a C.sub.3 to C.sub.4 alkynyl
group), more preferably an ethynyl, 1-propynyl or 2-propynyl
group.
In the present invention, "the amino group which may be substituted
(The substituent is a substituent selected from the substituent
Group D.)" is an amino group which may be substituted by the same
or different 1 to 2 substituent(s) selected from the group
consisting of the above-mentioned "C.sub.1 to C.sub.6 alkyl group",
the above-mentioned "C.sub.2 to C.sub.7 alkylcarbonyl group", the
above-mentioned "C.sub.2 to C.sub.7 alkoxycarbonyl group", the
above-mentioned "di(C.sub.1 to C.sub.6 alkyl)carbamoyl group" and
the above-mentioned "C.sub.1 to C.sub.6 alkylsulfonyl group", and
for example, it may be an amino, methylamino, ethylamino,
propylamino, isopropylamino, butylamino, isobutylamino,
s-butylamino, t-butylamino, pentylamino, isopentylamino,
(2-methylbutyl)amino, neopentylamino, (1-ethylpropyl)amino,
hexylamino, (4-methylpentyl)amino, (3-methylpentyl)amino,
(2-methylpentyl)amino, (1-methylpentyl)amino,
(3,3-dimethylbutyl)amino, (2,2-dimethylbutyl)amino,
(1,1-dimethylbutyl)amino, (1,2-dimethylbutyl)amino,
(1,3-dimethylbutyl)amino, (2,3-dimethylbutyl)amino,
(2-ethylbutyl)amino, dimethylamino, (methyl)(ethyl)amino,
diethylamino, dipropylamino, (methyl)(isopropyl)amino,
di(isopropyl)amino, dibutylamino, di(isobutyl)amino,
di(s-butyl)amino, di(t-butyl)amino, dipentylamino,
diisopentylamino, di(2-methylbutyl)amino, dineopentylamino,
di(1-ethylpropyl)amino, dihexylamino, di(4-methylpentyl)amino,
di(3-methylpentyl)amino, di(2-methylpentyl)amino,
di(1-methylpentyl)amino, di(3,3-dimethylbutyl)amino,
di(2,2-dimethylbutyl)amino, di(1,1-dimethylbutyl)amino,
di(1,2-dimethylbutyl)amino, di(1,3-dimethylbutyl)amino,
di(2,3-dimethylbutyl)amino, di(2-ethylbutyl)amino, acetylamino,
propionylamino, butanoylamino, (2-methylpropanoyl)amino,
pentanoylamino, (2,2-dimethylpropanoyl)amino,
(2,2-dimethylpentanoyl)amino, (2-methylbutanoyl)amino,
(3-methylbutanoyl)amino, hexanoylamino, heptanoyl amino,
(3,3-dimethylbutanoyl)amino, methoxycarbonylamino,
ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino,
butoxycarbonylamino, isobutoxycarbonylamino, s-butoxycarbonylamino,
t-butoxycarbonylamino, pentoxycarbonylamino,
isopentoxycarbonylamino, (2-methylbutoxycarbonyl)amino,
neopentoxycarbonylamino, (1-ethylpropoxycarbonyl)amino,
hexyloxycarbonylamino, (4-methylpentoxycarbonyl)amino,
(3-methylpentoxycarbonyl)amino, (2-methylpentoxycarbonyl)amino,
(1-methylpentoxycarbonyl)amino, (3,3-dimethylbutoxycarbonyl)amino,
(2,2-dimethylbutoxycarbonyl)amino,
(1,1-dimethylbutoxycarbonyl)amino,
(1,2-dimethylbutoxycarbonyl)amino,
(1,3-dimethylbutoxycarbonyl)amino,
(2,3-dimethylbutoxycarbonyl)amino, (2-ethylbutoxycarbonyl)amino,
dimethylcarbamoylamino, (methylethylcarbamoyl)amino,
diethylcarbamoylamino, dipropylcarbamoylamino,
dibutylcarbamoylamino, dihexylcarbamoylamino, methylsulfonylamino,
ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino,
butylsulfonylamino, t-butylsulfonylamino or hexylsulfonylamino,
preferably an amino group which may be substituted by the same or
different 1 to 2 C.sub.1 to C.sub.3 alkyl groups, or a C.sub.2 to
C.sub.4 alkylcarbonyl group, a C.sub.2 to C.sub.4 alkoxycarbonyl
group, a di(C.sub.1 to C.sub.3 alkyl)carbamoyl group or a C.sub.1
to C.sub.3 alkylsulfonyl group, more preferably an methylamino,
ethylamino, dimethylamino, diethylamino, acetylamino,
propionylamino, (2-methylpropanoyl)amino,
(2,2-dimethylpropanoyl)amino, methoxycarbonylamino,
ethoxycarbonylamino, dimethylcarbamoylamino, diethylcarbamoylamino,
methylsulfonylamino or ethylsulfonylamino group.
In the present invention, "the C.sub.1 to C.sub.6 haloalkoxy group"
is the above-mentioned "C.sub.1 to C.sub.6 alkoxy group"
substituted by the same or different 1 to 5 above-mentioned
"halogen atoms", and for example, it may be a chloromethoxy,
dichloromethoxy, trichloromethoxy, 1-chloroethoxy, 2-chloroethoxy,
2,2,2-trichloroethoxy, 1-chloropropoxy, 3-chloropropoxy,
1-chlorobutoxy, 4-chlorobutoxy, fluoromethoxy, difluoromethoxy,
trifluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy,
2,2,2-trifluoroethoxy, pentafluoroethoxy, fluorochloromethoxy,
bromomethoxy, 1-bromoethoxy, 2-bromoethoxy or iodomethoxy group,
preferably a C.sub.1 to C.sub.3 alkoxy group substituted by the
same or different 1 to 3 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom and a bromine atom,
more preferably a C.sub.1 to C.sub.2 alkoxy group substituted by
the same 1 to 3 fluorine atom(s) or chlorine atom(s), still further
preferably a fluoromethoxy, difluoromethoxy, trifluoromethoxy or
2,2,2-trichloroethoxy group, particularly preferably a
trifluoromethoxy group.
In the present invention, "the substituted C.sub.3 to C.sub.6
cycloalkyl group (The substituent is a substituent selected from
the substituent Group C.)" is the above-mentioned "C.sub.3 to
C.sub.6 cycloalkyl group" substituted by the same or different 1 to
5 substituent(s) selected from the group consisting of the
above-mentioned "halogen atom", the above-mentioned "C.sub.1 to
C.sub.6 alkyl group which may be substituted (The substituent is a
substituent selected from the substituent Group B.)", the
above-mentioned "C.sub.3 to C.sub.6 cycloalkyl group", the
above-mentioned "C.sub.2 to C.sub.6 alkenyl group", a cyano group,
the above-mentioned "C.sub.2 to C.sub.7 alkylcarbonyl group", a
benzoyl group, a carboxyl group, the above-mentioned "C.sub.2 to
C.sub.7 alkoxycarbonyl group", a carbamoyl group, the
above-mentioned "di(C.sub.1 to C.sub.6 alkyl)carbamoyl group", the
above-mentioned "phenyl group which may be substituted (The
substituent is a substituent selected from the substituent Group
A.)", the above-mentioned "5 or 6-membered heterocyclic group (the
heterocycle contains one nitrogen atom, oxygen atom or sulfur atom
in the ring, and may contain further 1 or 2 nitrogen atom(s).)",
the above-mentioned "amino group which may be substituted (The
substituent is a substituent selected from the substituent Group
D.)", a nitro group, a hydroxyl group, the above-mentioned "C.sub.1
to C.sub.6 alkoxy group", the above-mentioned "C.sub.1 to C.sub.6
haloalkoxy group", a phenoxy group, the above-mentioned "C.sub.1 to
C.sub.6 alkylthio group", a phenylthio group, the above-mentioned
"C.sub.1 to C.sub.6 alkylsulfinyl group" and the above-mentioned
"C.sub.1 to C.sub.6 alkylsulfonyl group", and for example, it may
be a fluorocyclopropyl, difluorocyclopropyl, chlorocyclopropyl,
dichlorocyclopropyl, bromocyclopropyl, dibromocyclopropyl,
iodocyclopropyl, methylcyclopropyl, ethylcyclopropyl,
propylcyclopropyl, isopropylcyclopropyl, butylcyclopropyl,
t-butylcyclopropyl, hexylcyclopropyl, cyclopropylcyclopropyl,
cyclobutylcyclopropyl, cyclopentylcyclopropyl,
(fluoromethyl)cyclopropyl, (chloromethyl)cyclopropyl,
(bromomethyl)cyclopropyl, (difluoromethyl)cyclopropyl,
(trifluoromethyl)cyclopropyl, (trichloromethyl)cyclopropyl,
(2,2,2-trifluoroethyl)cyclopropyl,
(2,2,2-trichloroethyl)cyclopropyl, vinylcyclopropyl,
(methoxymethyl)cyclopropyl, (ethoxymethyl)cyclopropyl,
(isopropoxymethyl)cyclopropyl, (methylthiomethyl)cyclopropyl,
(ethylthiomethyl)cyclopropyl, (isopropylthiomethyl)cyclopropyl,
(methylsulfinylmethyl)cyclopropyl,
(ethylsulfinylmethyl)cyclopropyl,
(methylsulfonylmethyl)cyclopropyl,
(ethylsulfonylmethyl)cyclopropyl, cyanocyclopropyl,
(1-methoxyiminoethyl)cyclopropyl, acetylcyclopropyl,
propionylcyclopropyl, benzoylcyclopropyl, carboxylcyclopropyl,
methoxycarbonylcyclopropyl, ethoxycarbonylcyclopropyl,
carbamoylcyclopropyl, (dimethylcarbamoyl)cyclopropyl,
(diethylcarbamoyl)cyclopropyl, phenylcyclopropyl,
(fluorophenyl)cyclopropyl, (chlorophenyl)cyclopropyl,
tolylcyclopropyl, furylcyclo-7 propyl, thienylcyclopropyl,
pyridylcyclopropyl, aminocyclopropyl, (methylamino)cyclopropyl,
(dimethylamino)cyclopropyl, (acetylamino)cyclopropyl,
(methoxycarbonylamino)cyclopropyl, (3,3-dimethylureido)cyclopropyl,
(methylsulfonylamino)cyclopropyl, nitrocyclopropyl,
hydroxycyclopropyl, methoxycyclopropyl, ethoxycyclopropyl,
(trifluoromethoxy)cyclopropyl, phenoxycyclopropyl,
methylthiocyclopropyl, ethylthiocyclopropyl, phenylthiocyclopropyl,
methylsulfinylcyclopropyl, ethylsulfinylcyclopropyl,
methylsulfonylcyclopropyl, ethylsulfonylcyclopropyl,
dimethylcyclopropyl, methyl(ethyl)cyclopropyl, diethylcyclopropyl,
biscyanocyclopropyl, trimethylcyclopropyl, tetramethylcyclopropyl,
pentamethylcyclopropyl, methylcyclobutyl, vinylcyclobutyl,
cyanocyclobutyl, carboxylcyclobutyl, acetylcyclobutyl,
methoxycarbonylcyclobutyl or aminocyclobutyl group, preferably a
C.sub.3 to C.sub.4 cycloalkyl group substituted by the same or
different 1 to 5 substituent(s) selected from the group consisting
of a fluorine atom, a chlorine atom, a bromine atom, a C.sub.1 to
C.sub.3 alkyl group, a C.sub.3 to C.sub.4 cycloalkyl group and a
cyano group, or substituted by "a C.sub.1 to C.sub.3 alkyl group
substituted by the same or different 1 to 3 substituent(s) selected
from the group consisting of a fluorine atom, a chlorine atom and a
bromine atom, or a C.sub.1 to C.sub.3 alkyl group substituted by a
C.sub.3 to C.sub.4 cycloalkyl group, a cyano group, a C.sub.2 to
C.sub.4 alkylcarbonyl group, a C.sub.2 to C.sub.4 alkoxycarbonyl
group, a phenyl group, a C.sub.1 to C.sub.3 alkoxy group, a C.sub.1
to C.sub.3 alkylthio group, a C.sub.1 to C.sub.3 alkylsulfinyl
group, a C.sub.1 to C.sub.3 alkylsulfonyl group, a C.sub.1 to
C.sub.2 alkylenedioxy group, an imino group or a C.sub.1 to C.sub.3
alkoxyimino group", a C.sub.2 to C.sub.4 alkenyl group, a C.sub.2
to C.sub.4 alkylcarbonyl group, a benzoyl group, a carboxyl group,
a C.sub.2 to C.sub.4 alkoxycarbonyl group, a carbamoyl group, a
di(C.sub.1 to C.sub.3 alkyl)carbamoyl group, "a phenyl group which
may be substituted by the same or different 1 to 3 substituent(s)
selected from the group consisting of a fluorine atom, a chlorine
atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl group, "a C.sub.1
to C.sub.3 alkyl group substituted by the same or different 1 to 3
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom and a bromine atom", a C.sub.3 to C.sub.4
cycloalkyl group, a cyano group and a tri(C.sub.1 to C.sub.3
alkyl)silyl group", a 5-membered heterocyclic group (the
heterocycle contains one nitrogen atom, oxygen atom or sulfur atom
in the ring.), "an amino group which may be substituted by the same
or different 1 to 2 C.sub.1 to C.sub.3 alkyl group, or by a C.sub.2
to C.sub.4 alkylcarbonyl group, a C.sub.2 to C.sub.4 alkoxycarbonyl
group, a di(C.sub.1 to C.sub.3 alkyl)carbamoyl group or a C.sub.1
to C.sub.3 alkylsulfonyl group", a nitro group, a hydroxyl group, a
C.sub.1 to C.sub.3 alkoxy group, a C.sub.1 to C.sub.3 haloalkoxy
group, a phenoxy group, a C.sub.1 to C.sub.3 alkylthio group, a
phenylthio group, a C.sub.1 to C.sub.3 alkylsulfinyl group or a
C.sub.1 to C.sub.3 alkylsulfonyl group, more preferably a
cyclopropyl group substituted by the same or different 1 to 3
substituent(s) selected from the group consisting of a chlorine
atom, a bromine atom, a C.sub.1 to C.sub.2 alkyl group, cyclopropyl
group and a cyano group, or by "a C.sub.1 to C.sub.2 alkyl group
substituted by a C.sub.1 to C.sub.2 alkyl group which is
substituted by the same 1 to 3 substituent(s) selected from the
group consisting of a chlorine atom and a bromine atom, or
substituted by a cyclopropyl group, a cyano group, a C.sub.2 to
C.sub.3 alkylcarbonyl group, a C.sub.2 to C.sub.3 alkoxycarbonyl
group, a phenyl group, a C.sub.1 to C.sub.2 alkoxy group, a C.sub.1
to C.sub.2 alkylthio group, a C.sub.1 to C.sub.2 alkylsulfinyl
group, a C.sub.1 to C.sub.2 alkylsulfonyl group, a
1,2-ethylenedioxy group, an imino group or a C.sub.1 to C.sub.2
alkoxyimino group", a C.sub.2 to C.sub.3 alkenyl group, a C.sub.2
to C.sub.3 alkylcarbonyl group, a benzoyl group, a carboxyl group,
a C.sub.2 to C.sub.3 alkoxycarbonyl group, a carbamoyl group, a
di(C.sub.1 to C.sub.2 alkyl)carbamoyl group, "a phenyl group which
may be substituted by the same or different 1 to 2 substituent(s)
selected from the group consisting of a chlorine atom, a bromine
atom, a C.sub.1 to C.sub.2 alkyl group, "a C.sub.1 to C.sub.2 alkyl
group substituted by the same 1 to 3 fluorine atom(s) or chlorine
atom(s)", a cyclopropyl group, a cyano group and a tri(C.sub.1 to
C.sub.2 alkyl)-silyl group", a furyl group, a thienyl group, "an
amino group which may be substituted by the same 1 to 2 C.sub.1 to
C.sub.2 alkyl group(s), or by a C.sub.2 to C.sub.3 alkylcarbonyl
group, a C.sub.2 to C.sub.3 alkoxycarbonyl group, a di(C.sub.1 to
C.sub.2 alkyl)carbamoyl group or a C.sub.1 to C.sub.2 alkylsulfonyl
group", a nitro group, a hydroxyl group, a C.sub.1 to C.sub.2
alkoxy group, a C.sub.1 to C.sub.2 haloalkoxy group, a phenoxy
group, a C.sub.1 to C.sub.2 alkylthio group, a phenylthio group, a
C.sub.1 to C.sub.2 alkylsulfinyl group or a C.sub.1 to C.sub.2
alkylsulfonyl group.
In the present invention, "the C.sub.4 to C.sub.10 bicycloalkyl
group" is a bicyclic hydrocarbon having 4 to 10 carbon atoms, and
for example, it may be a bicyclobutyl, bicyclepentyl, bicyclohexyl,
bicycloheptyl, bicyclooctyl, bicyclononyl or bicyclodecyl group,
preferably a bicyclehexyl or bicycleheptyl group, more preferably a
bicycle[3.1.0]hexyl or bicyclo[4.1.0]heptyl group, still further
preferably a bicyclo[3.1.0]hexan-6-yl group.
In the present invention, "the phenylsulfonyl group which may be
substituted (The substituent is a substituent selected from the
substituent Group A.)" is a phenylsulfonyl group which may be
substituted by the same or different 1 to 5 substituent(s) selected
from the group consisting of the above-mentioned "halogen atom",
the above-mentioned "C.sub.1 to C.sub.6 alkyl group", the
above-mentioned "C.sub.1 to C.sub.6 haloalkyl group", the
above-mentioned "C.sub.3 to C.sub.6 cycloalkyl group", a cyano
group and the above-mentioned "tri(C.sub.1 to C.sub.6 alkyl)silyl
group", and for example, it may be a phenylsulfonyl,
fluorophenylsulfonyl, difluorophenylsulfonyl,
trifluorophenylsulfonyl, chlorophenylsulfonyl,
dichlorophenylsulfonyl, trichlorophenylsulfonyl,
fluorochlorophenylsulfonyl, methylphenylsulfonyl,
dimethylphenylsulfonyl, trimethylphenylsulfonyl,
tetramethylphenylsulfonyl, pentamethylphenylsulfonyl,
ethylphenylsulfonyl, fluoro(methyl)phenylsulfonyl,
chloro(methyl)phenylsulfonyl, bromo(methyl)phenylsulfonyl,
cyclopropylphenylsulfonyl, cyclopropyl(fluoro)phenylsulfonyl,
chloro(cyclopropyl)phenylsulfonyl,
cyclopropyl(methyl)phenylsulfonyl, (trifluoromethyl)phenylsulfonyl
or fluoro(trifluoromethyl)phenylsulfonyl group, preferably a
phenylsulfonyl group which may be substituted by the same or
different 1 to 3 substituent(s) selected from the group consisting
of a fluorine atom, a chlorine atom, a bromine atom, a C.sub.1 to
C.sub.3 alkyl group, "a C.sub.1 to C.sub.3 alkyl group substituted
by the same or different 1 to 3 substituent(s) selected from the
group consisting of a fluorine atom, a chlorine atom and a bromine
atom", a C.sub.3 to C.sub.4 cycloalkyl group, a cyano group and a
tri(C.sub.1 to C.sub.3 alkyl)silyl group, more preferably a
phenylsulfonyl, chlorophenylsulfonyl, methylphenylsulfonyl,
trifluorophenylsulfonyl or cyanophenylsulfonyl group.
In the present invention, "the di(C.sub.1 to C.sub.6
alkyl)sulfamoyl group" is a sulfamoyl group in which the same or
different 2 above-mentioned "C.sub.1 to C.sub.6 alkyl groups" are
bonded to the nitrogen atom, and for example, it may be a
dimethylsulfamoyl, methylethylsulfamoyl, diethylsulfamoyl,
dipropylsulfamoyl, dibutylsulfamoyl or dihexylsulfamoyl, preferably
a sulfamoyl group to which the same or different 2 C.sub.1 to
C.sub.3 alkyl groups are bonded, more preferably a
dimethylsulfamoyl or diethylsulfamoyl group, still further
preferably a dimethylsulfamoyl group.
In the present invention, "the 3- to 6-membered heterocyclic group
which may be substituted (the heterocycle contains one nitrogen
atom, oxygen atom or sulfur atom in the ring, and may contain
further 1 or 2 nitrogen atom(s), or may be fused with a benzene
ring. The substituent is a substituent selected from the
substituent Group E.)" is "a 3- to 6-membered heterocyclic group
which contains one nitrogen atom, oxygen atom or sulfur atom as a
hetero atom, and may contain further 1 to 2 nitrogen atom(s)" which
may be substituted by the same or different 1 to 3 substituent(s)
selected from the group consisting of the above-mentioned "halogen
atom", the above-mentioned "C.sub.1 to C.sub.6 alkyl group" and the
above-mentioned "C.sub.1 to C.sub.6 haloalkyl group", or by a
hydroxyl group, the above-mentioned "phenylsulfonyl group which may
be substituted (The substituent is a substituent selected from the
substituent Group A.)" or the above-mentioned "di(C.sub.1 to
C.sub.6 alkyl)sulfamoyl group", or may be fused with a benzene
ring, preferably "a 3- to 6-membered heterocyclic group which
contains one nitrogen atom, oxygen atom or sulfur atom as a hetero
atom, and may contain further one nitrogen atom" which may be
substituted by the same or different 1 to 2 substituent(s) selected
from the group consisting of a fluorine atom, a chlorine atom, a
bromine atom, a C.sub.1 to C.sub.3 alkyl group and "a C.sub.1 to
C.sub.3 alkyl group substituted by the same or different 1 to 3
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom and a bromine atom", or may be substituted by
a hydroxyl group, "a phenylsulfonyl group which may be substituted
by the same or different 1 to 3 substituent(s) selected from the
group consisting of a fluorine atom, a chlorine atom, a bromine
atom, a C.sub.1 to C.sub.3 alkyl group, "a C.sub.1 to C.sub.3 alkyl
group substituted by the same or different 1 to 3 substituent(s)
selected from the group consisting of a fluorine atom, a chlorine
atom and a bromine atom", a C.sub.3 to C.sub.4 cycloalkyl group, a
cyano group and a tri(C.sub.1 to C.sub.3 alkyl)silyl group" or "a
sulfamoyl group to which the same or different 2 C.sub.1 to C.sub.3
alkyl groups are bonded", or may be fused with a benzene ring, more
preferably an aziridine, oxiranyl, oxetanyl, pyrrolyl, furyl,
thienyl, pyrazolyl, thiazolyl, pyridyl, benzimidazolyl or
benzothiazolyl, each of which may be substituted by the same 1 to 2
substituent(s) selected from the group consisting of a chlorine
atom, a bromine atom, methyl group, ethyl group and trifluoromethyl
group, or may be substituted by a hydroxyl group, phenylsulfonyl
group, tolylsulfonyl group or dimethylsulfamoyl group, still
further preferably a thienyl, pyrazolyl, thiazolyl group which may
be substituted by the same or different 1 to 2 substituent(s)
selected from the group consisting of a chlorine atom, methyl group
and trifluoromethyl group.
In the present invention, "the (C.sub.1 to C.sub.6 alkoxy)C.sub.1
to C.sub.6 alkoxy group" is an alkoxy group having 1 to 6 carbon
atoms to which an alkoxy group having 1 to 6 carbon atoms is
bonded, and for example, it may be a methoxymethoxy, ethoxymethoxy,
propoxymethoxy, butoxymethoxy, s-butoxymethoxy, t-butoxymethoxy,
pentyloxymethoxy, hexyloxymethoxy, methoxyethoxy, ethoxyethoxy,
propoxyethoxy, butoxyethoxy, methoxypropoxy, methoxybutoxy,
methoxypentyloxy or methoxyhexyloxy group, preferably an alkoxy
group having 1 to 3 carbon atoms to which an alkoxy group having 1
to 3 carbon atoms is substituted, more preferably a methoxyethoxy,
ethoxyethoxy or ethoxymethoxy group.
In the present invention, "a phenoxy group which may be substituted
(The substituent is a hydroxyl group or a pyridazinyloxy group
substituted by a substituent(s) selected from the group consisting
of a halogen atom and a C.sub.1 to C.sub.6 alkoxy group.)" is a
phenoxy group which may be substituted by one hydroxyl group, or a
phenoxy group substituted by a pyridazinyloxy group which is
substituted by the same or different 1 to 3 substituent(s) selected
from the group consisting of the above-mentioned "halogen atom" and
the above-mentioned "C.sub.1 to C.sub.6 alkoxy group", preferably a
hydroxyphenoxy group, or a phenoxy group substituted by a
pyridazinyloxy group which is substituted by the same or different
1 to 2 substituent(s) selected from the group consisting of a
fluorine atom, a chlorine atom, a bromine atom and C.sub.1 to
C.sub.3 alkoxy group, more preferably a phenoxy group substituted
by a pyridazinyloxy group which is substituted by each one of a
chlorine atom, and a methoxy or ethoxy group.
In the present invention, "the 5- to 6-membered heterocycloxy group
which may be substituted (the heterocycle contains one nitrogen
atom, oxygen atom or sulfur atom in the ring, and may contain
further 1 or 2 nitrogen atom(s). The substituent is a substituent
selected from the substituent Group E.)" is "a 5- to 6-membered
heterocycloxy group which contains one nitrogen atom, oxygen atom
or sulfur atom as a heteroatom, and may contain further 1 to 2
nitrogen atom(s)" which may be substituted by the same or different
1 to 2 substituent(s) selected from the group consisting of the
above-mentioned "halogen atom", the above-mentioned "C.sub.1 to
C.sub.6 alkyl group", the above-mentioned "C.sub.1 to C.sub.6
haloalkyl group", a hydroxyl group, the above-mentioned
"phenylsulfonyl group which may be substituted (The substituent is
a substituent selected from the substituent Group A.)" and the
above-mentioned "di(C.sub.1 to C.sub.6 alkyl)sulfamoyl group",
preferably "a 5- to 6-membered heterocycloxy group which contains
one nitrogen atom, oxygen atom or sulfur atom as a heteroatom, and
may contain further one nitrogen atom" which may be substituted by
the same or different 1 to 2 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.3 alkyl group, "a C.sub.1 to C.sub.3 alkyl group
substituted by the same or different 1 to 3 substituent(s) selected
from the group consisting of a fluorine atom, a chlorine atom and a
bromine atom", a hydroxyl group, "a phenylsulfonyl group which may
be substituted by the same or different 1 to 3 substituent(s)
selected from the group consisting of a fluorine atom, a chlorine
atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl group, "a C.sub.1
to C.sub.3 alkyl group substituted by the same or different 1 to 3
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom and a bromine atom", a C.sub.3 to C.sub.4
cycloalkyl group, a cyano group and a tri(C.sub.1 to C.sub.3
alkyl)silyl group" and "a sulfamoyl group to which the same or
different two C.sub.1 to C.sub.3 alkyl groups are bonded", more
preferably a pyridyloxy, pyrrolyloxy, furyloxy, thienyloxy,
pyrazolyloxy, thiazolyloxy, pyrimidyloxy, pyrazinyloxy or a
pyridazinyloxy group, each of which may be substituted by 1 to 2
different substituents selected from the group consisting of a
chlorine atom, a bromine atom, a methyl group, an ethyl group, a
trifluoromethyl group, a hydroxyl group, a phenylsulfonyl group, a
tolylsulfonyl group and a dimethylsulfamoyl group, still further
preferably a pyridazinyloxy group which may be substituted by a
chlorine atom and a hydroxyl group.
In the present invention, "the phenylsulfonyloxy group which may be
substituted (The substituent is a substituent selected from the
substituent Group A.)" is a phenylsulfonyloxy group which may be
substituted by the same or different 1 to 5 substituent(s) selected
from the group consisting of the above-mentioned "halogen atom",
the above-mentioned "C.sub.1 to C.sub.6 alkyl group", the
above-mentioned "C.sub.1 to C.sub.6 haloalkyl group", the
above-mentioned "C.sub.3 to C.sub.6 cycloalkyl group", a cyano
group and the above-mentioned "tri(C.sub.1 to C.sub.6 alkyl)silyl
group", and for example, it may be a phenylsulfonyloxy,
fluorophenylsulfonyloxy, difluorophenylsulfonyloxy,
trifluorophenylsulfonyloxy, chlorophenylsulfonyloxy,
dichlorophenylsulfonyloxy, trichlorophenylsulfonyloxy,
fluorochlorophenylsulfonyloxy, methylphenylsulfonyloxy,
dimethylphenylsulfonyloxy, trimethylphenylsulfonyloxy,
tetramethylphenylsulfonyloxy, pentamethylphenylsulfonyloxy,
ethylphenylsulfonyloxy, fluoro(methyl)phenylsulfonyloxy,
chloro(methyl)phenylsulfonyloxy, bromo(methyl)phenylsulfonyloxy,
cyclopropylphenylsulfonyloxy, cyclopropyl(fluoro)phenylsulfonyloxy,
chloro(cyclopropyl)phenylsulfonyloxy,
cyclopropyl(methyl)phenylsulfonyloxy,
(trifluoromethyl)phenylsulfonyloxy or
fluoro(trifluoromethyl)phenylsulfonyloxy group, preferably a
phenylsulfonyloxy group which may be substituted by the same or
different 1 to 3 substituent(s) selected from the group consisting
of a fluorine atom, a chlorine atom, a bromine atom, a C.sub.1 to
C.sub.3 alkyl group, "a C.sub.1 to C.sub.3 alkyl group substituted
by the same or different 1 to 3 substituent(s) selected from the
group consisting of a fluorine atom, a chlorine atom and a bromine
atom", a C.sub.3 to C.sub.4 cycloalkyl group, a cyano group and a
tri(C.sub.1 to C.sub.3 alkyl)silyl group, more preferably a
phenylsulfonyloxy, chlorophenylsulfonyloxy,
methylphenylsulfonyloxy, trifluorophenylsulfonyloxy or
cyanophenylsulfonyloxy group.
In R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 according to the
present invention, "the 3- to 6-membered cyclic hydrocarbon group
which may be substituted, which is formed by the adjacent two of
them with carbon atoms to which the respective substituents are
bonded (the cyclic hydrocarbon may be interrupted by 1 to 2 hetero
atom(s) selected from the group consisting of a nitrogen atom, an
oxygen atom and a sulfur atom. The substituent is a halogen atom, a
C.sub.1 to C.sub.6 alkyl group, a hydroxy-C.sub.1 to C.sub.6 alkyl
group, a C.sub.1 to C.sub.6 alkoxy group, an oxo group, a
hydroxyimino group or a C.sub.1 to C.sub.6 alkoxyimino group, and
when the C.sub.1 to C.sub.6 alkyl group is substituted, it may form
another 3-membered ring by binding with the other C.sub.1 to
C.sub.6 alkyl group or a carbon atom(s)in the cyclic hydrocarbon.)"
is a saturated or unsaturated 3- to 6-membered cyclic hydrocarbon
group which may be substituted by the same or different 1 to 4
substituent(s) selected from the group consisting of the
above-mentioned "halogen atom", the above-mentioned "C.sub.1 to
C.sub.6 alkyl group", the above-mentioned "C.sub.1 to C.sub.6 alkyl
group" substituted by 1 to 2 hydroxyl group(s), the above-mentioned
"C.sub.1 to C.sub.6 alkoxy group", an oxo group, a hydroxyimino
group and the above-mentioned "C.sub.1 to C.sub.6 alkoxyimino
group", and may be interrupted by the same or different 1 to 2
hetero atom(s) selected from the group consisting of a nitrogen
atom, an oxygen atom and a sulfur atom, and further may form a
cyclopropane ring on the cyclic hydrocarbon group, preferably a
group represented by --CH.sub.2--, --CH.sub.2CH.sub.2--,
--CH.sub.2CH.sub.2CH.sub.2--, --CH (CH.sub.3) CH.sub.2CH.sub.2--,
--CH.sub.2CH (CH.sub.3) CH.sub.2--,
--C(CH.sub.3).sub.2CH.sub.2CH.sub.2--, --CH.sub.2C(CH.sub.3)
.sub.2CH.sub.2--, --CH (OCH.sub.3) CH.sub.2CH.sub.2--,
--C(OCH.sub.3).sub.2CH.sub.2CH.sub.2--, --CH.sub.2C
(OCH.sub.3).sub.2CH.sub.2--, --C(.dbd.O) CH.sub.2CH.sub.2--,
--CH.sub.2C(.dbd.O) CH.sub.2--, --C(.dbd.NOCH.sub.3)
CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --CH
(CH.sub.3) CH.sub.2CH.sub.2CH.sub.2--,
--C(CH.sub.3).sub.2CH.sub.2CH.sub.2CH.sub.2--, --CH (OCH.sub.3)
CH.sub.2CH.sub.2CH.sub.2--, --CH.dbd.CH--CH.dbd.CH--,
--OCH.sub.2CH.sub.2--, --OCH (CH.sub.3) CH.sub.2--,
--OCH.sub.2CH(CH.sub.3)--, --OC(CH.sub.3).sub.2CH.sub.2--,
--OCH.dbd.CH--, --OC(CH.sub.3).dbd.CH--, --OCH.dbd.C(CH.sub.3)--,
--SCH.dbd.CH--, --N.dbd.CH--CH.dbd.CH--, --OCH.sub.2O--, --OCH
(CH.sub.3)O--, --OC(CH.sub.3).sub.2O--, --OCF.sub.2O--,
--OCH.sub.2CH.sub.2O--, --OCH.dbd.N--, --OC(CH.sub.3) .dbd.N--,
##STR00003## more preferably a group represented by
--CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2----CH (CH.sub.3)
CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--,
--CH.dbd.CH--CH.dbd.CH--, --OCH.sub.2CH.sub.2--, --OCH.dbd.CH--,
--OCH.dbd.C(CH.sub.3)--, --SCH.dbd.CH--, --N.dbd.CH--CH.dbd.CH--,
--OCH.sub.2O--, --OCH.sub.2CH.sub.2O--,
##STR00004## still further preferably a group represented by
--CR.sub.2CR.sub.2CR.sub.2--, --CH (CH.sub.3) CH.sub.2CH.sub.2--,
--OCH.sub.2CH.sub.2--, --OCH.dbd.CH-- or
##STR00005##
The compound (I) of the present invention can be made a salt to be
generally used in agricultural chemicals, and for example, it can
be made an alkali metal salt, an alkaline earth metal salt or an
ammonium salt, and when a basic portion exists in the molecule, it
can be made a salt, for example, a sulfate, hydrochloride, nitrate,
phosphate, or the like. These salts are included in the present
invention so long as they can be used as a herbicide for
agricultural and horticultural chemicals.
In the present invention, "the alkali metal salt" may be, for
example, a sodium salt, potassium salt or lithium salt, preferably
a sodium salt or potassium salt.
In the present invention, "the alkaline earth metal salt" may be,
for example, a calcium salt or magnesium salt, preferably a calcium
salt.
A solvate of the compounds of the present invention is also
included in the present invention.
In the compounds of the present invention, there are compounds
having an asymmetric carbon(s), and in that case, the present
invention also includes a kind of optical isomers and a mixture of
several kinds of optical isomers with an optional ratio.
In the present invention, "ester derivative" is a compound in which
an acyl group bonds to an oxygen atom of a hydroxyl group bonded at
the 4-position of the pyridazine ring, and for example, a compound
to which is/are bonded a C.sub.2 to. C.sub.15 alkylcarbonyl group
which may be substituted [The substituent is the same or different
1 to 3 substituent(s) selected from the group consisting of a
halogen atom, a C.sub.1 to C.sub.6 alkoxy group, a C.sub.2 to
C.sub.7 alkoxycarbonyl group, a C.sub.2 to C.sub.6
alkenyloxycarbonyl group which may be substituted {The substituent
is the same or different 1 to 3 substituent(s) selected from the
group consisting of a C.sub.3 to C.sub.6 cycloalkyl group, a cyano
group and a benzoyl group which may be substituted (The substituent
is the same or different 1 to 3 substituent(s) selected from the
group consisting of a halogen atom, a C.sub.1 to C.sub.6 alkyl
group, a C.sub.1 to C.sub.3 haloalkyl group, a C.sub.2 to C.sub.7
alkoxycarbonyl group, a nitro group and a C.sub.1 to C.sub.3
alkylsulfonyl group.).}, a C.sub.3 to C.sub.6
cycloalkenyloxycarbonyl group which may be substituted {The
substituent is the same or different 1 to 2 substituent(s) selected
from the group consisting of an oxo group and a benzoyl group which
may be substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.3
haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group, a nitro
group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).}, a 5 or
6-membered heterocycloxycarbonyl group which may be substituted
{the heterocycle contains one nitrogen atom, oxygen atom or sulfur
atom in the ring, and may contain further 1 or 2 nitrogen atom(s).
The substituent is the same or different 1 to 3 substituent(s)
selected from the group consisting of a halogen atom, a C.sub.1 to
C.sub.6 alkyl group, a phenoxy group which may be substituted (The
substituent is the same or deferent 1 to 3 substituent(s) selected
from the group consisting of a halogen atom, a C.sub.1 to C.sub.6
alkyl group, a C.sub.1 to C.sub.3 haloalkyl group, a C.sub.3 to
C.sub.6 cycloalkyl group and a C.sub.2 to C.sub.7 alkoxycarbonyl
group.), a 2,3-dihydro-1H-indenyloxy group and a benzoyl group
which may be substituted (The substituent is the same or different
1 to 3 substituent(s) selected from the group consisting of a
halogen atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to
C.sub.3 haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group,
a nitro group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).}, a
phenyl group which may be substituted (The substituent is the same
or different 1 to 3 substituent(s) selected from the group
consisting of a halogen atom, a C.sub.1 to C.sub.6 alkyl group, a
C.sub.1 to C.sub.3 haloalkyl group and a C.sub.2 to C.sub.7
alkoxycarbonyl group.), a phenoxy group and a C.sub.1 to C.sub.6
alkylthio group.], a C.sub.4 to C.sub.7 cycloalkylcarbonyl group,
an adamantylcarbonyl group, a C.sub.3 to C.sub.7 alkenylcarbonyl
group which may be substituted (The substituent is the same or
different 1 to 2 substituent(s) selected from the group consisting
of a halogen atom and a phenyl group.), a C.sub.3 to C.sub.7
alkynylcarbonyl group, a benzoyl group which may be substituted
(The substituent is the same or different 1 to 3 substituent(s)
selected from the group consisting of a halogen atom, a C.sub.1 to
C.sub.6 alkyl group which may be substituted (The substituent is
the same or different 1 to 3 substituent(s) selected from the group
consisting of a halogen atom and a phenyl group.), a cyano group, a
C.sub.2 to C.sub.7 alkylcarbonyl group, a C.sub.2 to C.sub.7
alkoxycarbonyl group, a C.sub.3 to C.sub.7 alkenyloxycarbonyl group
which may be substituted {The substituent is the same or different
1 to 3 substituent(s) selected from the group consisting of a
C.sub.3 to C.sub.6 cycloalkyl group, a cyano group and a benzoyl
group which may be substituted (The substituent is the same or
different 1 to 3 substituent(s) selected from the group consisting
of a halogen atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to
C.sub.3 haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group,
a nitro group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).}, a
C.sub.4 to C.sub.7 cycloalkenyloxycarbonyl group which may be
substituted {The substituent is the same or different 1 to 2
substituent(s) selected from the group consisting of an oxo group
and a benzoyl group which may be substituted (The substituent is
the same or different 1 to 3 substituent(s) selected from the group
consisting of a halogen atom, a C.sub.1 to C.sub.6 alkyl group, a
C.sub.1 to C.sub.3 haloalkyl group, a C.sub.2 to C.sub.7
alkoxycarbonyl group, a nitro group and a C.sub.1 to C.sub.3
alkylsulfonyl group.).}, a phenyl group, a nitro group, a C.sub.1
to C.sub.6 alkoxy group which may be substituted (The substituent
is the same or different 1 to 3 substituent(s) selected from the
group consisting of a halogen atom and a phenyl group.), a phenoxy
group, a 5 or 6-membered heterocyclic oxycarbonyl group which may
be substituted {the heterocycle contains one nitrogen atom, oxygen
atom or sulfur atom in the ring, and may contain further 1 or 2
nitrogen atom(s). The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a phenoxy group which may
be substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.3
haloalkyl group, a C.sub.3 to C.sub.6 cycloalkyl group and a
C.sub.2 to C.sub.7 alkoxycarbonyl group.), a
2,3-dihydro-1H-indenyloxy group and a benzoyl group which may be
substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.3
haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group, a nitro
group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).} and a 5 or
6-membered heterocycloxysulfonyl group which may be substituted
{the heterocycle contains one nitrogen atom, oxygen atom or sulfur
atom in the ring, and may contain further 1 or 2 nitrogen atom(s).
The substituent is the same or different 1 to 3 substituent(s)
selected from the group consisting of a halogen atom, a C.sub.1 to
C.sub.6 alkyl group, a phenoxy group which may be substituted (The
substituent is the same or different 1 to 3 substituent(s) selected
from the group consisting of a halogen atom, a C.sub.1 to C.sub.6
alkyl group, a C.sub.1 to C.sub.3 haloalkyl group, a C.sub.3 to
C.sub.6 cycloalkyl group and a C.sub.2 to C.sub.7 alkoxycarbonyl
group.), a 2,3-dihydro-1H-indenyloxy group and a benzoyl group
which may be substituted (The substituent is the same or different
1 to 3 substituent(s) selected from the group consisting of a
halogen atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to
C.sub.3 haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group,
a nitro group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).}.], a
naphthoyl group, a 3- to 6-membered heterocyclic carbonyl group
which may be substituted {the heterocycle contains one nitrogen
atom, oxygen atom or sulfur atom in the ring, and may contain
further 1 or 2 nitrogen atom(s), or may form a 5- to 6-membered
spiro ring containing 1 to 2 oxygen atom(s) on an optional carbon
atom in the heterocycle. The substituent is the same or different 1
to 3 substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group which may be substituted
(The substituent is the same or different 1 to 3 substituent(s)
selected from the group consisting of a halogen atom and a phenyl
group.), a C.sub.2 to C.sub.7 alkylcarbonyl group, a C.sub.2 to
C.sub.7 alkoxycarbonyl group, a phenyl group which may be
substituted (The substituent is the same or different 1 to 3
halogen atom(s).), a nitro group, a hydroxyl group, a C.sub.1 to
C.sub.6 alkoxy group, a phenoxy group, a C.sub.1 to C.sub.6
alkylthio group, a C.sub.2 to C.sub.6 alkenylthio group and a
phenylthio group.}, a 7 to 14-membered fused bi- or tri-cyclic
heterocyclic carbonyl group which may be substituted (The
heterocycle contains one nitrogen atom, oxygen atom or sulfur atom
in the ring, and may contain further 1 to 2 nitrogen atom(s) or
oxygen atom(s). The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen atom
and a C.sub.1 to C.sub.6 alkyl group.), a 5 or 6-membered
heterocycle carbonylcarbonyl group (The heterocycle contains one
nitrogen atom, oxygen atom or sulfur atom in the ring, and may
contain further 1 or 2 nitrogen atom(s).), a C.sub.2 to C.sub.7
alkoxycarbonyl group which may be substituted (The substituent is
the same or different 1 to 3 substituent(s) selected from the group
consisting of a halogen atom, a C.sub.1 to C.sub.6 alkoxy group and
a phenyl group.), a C.sub.3 to C.sub.7 alkenyloxycarbonyl group, a
phenoxycarbonyl group which may be substituted (The substituent is
the same or different 1 to 3 substituent(s) selected from the group
consisting of a halogen atom, a C.sub.1 to C.sub.6 alkyl group, a
cyano group, a C.sub.2 to C.sub.7 alkylcarbonyl group, a C.sub.2 to
C.sub.7 alkoxycarbonyl group, a nitro group and a C.sub.1 to
C.sub.6 alkoxy group.), a fused polycyclic hydrocarbyloxycarbonyl
group, a 5 or 6-membered heterocycloxycarbonyl group which may be
substituted {The heterocycle contains one nitrogen atom, oxygen
atom or sulfur atom in the ring, and may contain further 1 or 2
nitrogen atom(s). The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a phenoxy group which may
be substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.3
haloalkyl group, a C.sub.3 to C.sub.6 cycloalkyl group and a
C.sub.2 to C.sub.7 alkoxycarbonyl group.), a
2,3-dihydro-1H-indenyloxy group and a benzoyl group which may be
substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.3
haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group, a nitro
group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).}, a carbamoyl
group which may be substituted {The substituent is the same or
different 1 to 3 substituent(s) selected from the group consisting
of a C.sub.1 to C.sub.6 alkyl group which may be substituted (The
substituent is the same or different 1 to 3 substituent(s) selected
from the group consisting of a halogen atom, a C.sub.2 to C.sub.7
alkoxycarbonyl group, a cyano group, a phenyl group and a C.sub.1
to C.sub.6 alkoxy group.), a C.sub.3 to C.sub.6 alkenyl group, a
phenyl group, a C.sub.2 to C.sub.7 alkylcarbonyl group, a C.sub.2
to C.sub.7 alkoxycarbonyl group and a C.sub.1 to C.sub.6 alkoxy
group.}, a (C.sub.1 to C.sub.6 alkylthio)carbonyl group, a
(phenylthio)carbonyl group, a C.sub.1 to C.sub.8 alkylsulfonyl
group which may be substituted (The substituent is the same or
different 1 to 3 halogen atom(s).), a phenylsulfonyl group which
may be substituted [The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a cyano group, a C.sub.2 to
C.sub.7 alkylcarbonyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl
group, a nitro group, a C.sub.1 to C.sub.6 alkoxy group, a C.sub.2
to C.sub.6 alkenyloxysulfonyl group which may be substituted {The
substituent is the same or different 1 to 3 substituent(s) selected
from the group consisting of a C.sub.3 to C.sub.6 cycloalkyl group,
a cyano group and a benzoyl group which may be substituted (The
substituent is the same or different 1 to 3 substituent(s) selected
from the group consisting of a halogen atom, a C.sub.1 to C.sub.6
alkyl group, a C.sub.1 to C.sub.3 haloalkyl group, a C.sub.2 to
C.sub.7 alkoxycarbonyl group, a nitro group and a C.sub.1 to
C.sub.3 alkylsulfonyl group.).}, a C.sub.3 to C.sub.6
cycloalkenyloxysulfonyl group which may be substituted {The
substituent is the same or different 1 to 2 substituent(s) selected
from the group consisting of an oxo group and a benzoyl group which
may be substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.3
haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group, a nitro
group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).} and a 5 or
6-membered heterocycloxysulfonyl group which may be substituted
{The heterocycle contains one nitrogen atom, oxygen atom or sulfur
atom in the ring, and may contain further 1 or 2 nitrogen atom(s).
The substituent is the same or different 1 to 3 substituent(s)
selected from the group consisting of a halogen atom, a C.sub.1 to
C.sub.6 alkyl group, a phenoxy group which may be substituted (The
substituent is the same or different 1 to 3 substituent(s) selected
from the group consisting of a halogen atom, a C.sub.1 to C.sub.6
alkyl group, a C.sub.1 to C.sub.3 haloalkyl group, a C.sub.3 to
C.sub.6 cycloalkyl group and a C.sub.2 to C.sub.7 alkoxycarbonyl
group.), a 2,3-dihydro-1H-indenyloxy group and a benzoyl group
which may be substituted (The substituent is the same or different
1 to 3 substituent(s) selected from the group consisting of a
halogen atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to
C.sub.3 haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group,
a nitro group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).}.], a
5 or 6-membered heterocycloxysulfonyl group which may be
substituted {The heterocycle contains one nitrogen atom, oxygen
atom or sulfur atom in the ring, and may contain further 1 or 2
nitrogen atom(s). The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a phenoxy group which may
be substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.3
haloalkyl group, a C.sub.3 to C.sub.6 cycloalkyl group and a
C.sub.2 to C.sub.7 alkoxycarbonyl group.), a
2,3-dihydro-1H-indenyloxy group and a benzoyl group which may be
substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a halogen
atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.1 to C.sub.3
haloalkyl group, a C.sub.2 to C.sub.7 alkoxycarbonyl group, a nitro
group and a C.sub.1 to C.sub.3 alkylsulfonyl group.).}, a
di(C.sub.1 to C.sub.6 alkyl)sulfamoyl group, a C.sub.1 to C.sub.6
alkoxysulfonyl group, a di(C.sub.1 to C.sub.6 alkyl)phosphoryl
group, a tri(C.sub.1 to C.sub.6 alkyl)silyl group or a
triphenylsilyl group, preferably a compound to which bonded
is/arena C.sub.2 to C.sub.10 alkylcarbonyl group, a benzoyl group
which may be substituted (The substituent is the same or different
1 to 2 substituent(s) selected from the group consisting of a
fluorine atom, a chlorine atom, a bromine atom, a C.sub.1 to
C.sub.3 alkyl group, a C.sub.1 to C.sub.3 alkoxy group or a
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yloxycarbonyl
group.), a pyrrolidinylcarbonyl group, azetidinylcarbonyl group,
morpholinyl carbonyl group, a C.sub.2 to C.sub.5 alkoxycarbonyl
group which may be substituted (The substituent is the same or
different 1 to 3 substituent(s) selected from the group consisting
of a fluorine atom, a chlorine atom and a bromine atom.), a
di(C.sub.1 to C.sub.3 alkyl)carbamoyl group, a (C.sub.1 to C.sub.3
alkyl) (C.sub.1 to C.sub.3 alkoxy)carbamoyl group, a C.sub.1 to
C.sub.3 alkylsulfonyl group which may be substituted (The
substituent is the same or different 1 to 3 substituent(s) selected
from the group consisting of a fluorine atom, a chlorine atom and a
bromine atom.) or a phenylsulfonyl group which may be substituted
(The substituent is the same or different 1 to 2 substituent(s)
selected from the group consisting of a fluorine atom, a chlorine
atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl group, a
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yloxysulfonyl
group and a nitro group.), more preferably a compound to which
bonded is/are a C.sub.2 to C.sub.4 alkylcarbonyl group, a benzoyl
group which may be substituted (The substituent is a methyl group
or a
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yloxycarbonyl
group.), a 1-acetidinylcarbonyl group, a 4-morpholinylcarbonyl
group, a C.sub.2 to C.sub.3 alkoxycarbonyl group which may be
substituted (The substituent is 1 to 3 chlorine atom(s).), a
dimethylcarbamoyl group, a methoxy(methyl)carbamoyl group, a
C.sub.1 to C.sub.3 alkylsulfonyl group which may be substituted
(The substituent is 1 to 3 fluorine atom(s).) or a phenylsulfonyl
group which may be substituted (The substituent is a chlorine atom,
a methyl group, a
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yloxysulfonyl
group or a nitro group.).
(a) In the present invention, R.sup.1 is preferably a hydrogen
atom, a fluorine atom, a chlorine atom, a bromine atom, C.sub.1 to
C.sub.3 alkyl group, C.sub.1 to C.sub.3 haloalkyl group (The
halogen atom is 1 to 3 fluorine atom(s).), cyclopropyl group,
C.sub.2 to C.sub.3 alkenyl group, a cyano group, C.sub.2 to C.sub.4
alkylcarbonyl group, di(C.sub.1 to C.sub.3 alkyl)carbamoyl group, a
phenyl group which may be substituted {The substituent is the same
or different 1 to 2 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.3 alkyl group, a C.sub.1 to C.sub.3 haloalkyl
group (The halogen atom is the same or different 1 to 3 halogen
atom(s) selected from the group consisting of a fluorine atom, a
chlorine atom and a bromine atom.), a cyclopropyl group, a cyano
group and a tri(C.sub.1 to C.sub.3 alkyl)silyl group.}, a furyl
group, a thienyl group, a C.sub.1 to C.sub.3 alkoxy group, a
phenoxy group which may be substituted {The substituent is the same
or different 1 to 2 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.3 alkyl group, a C.sub.1 to C.sub.3 haloalkyl
group (The halogen atom is 1 to 3 fluorine atom(s).), a cyclopropyl
group, a cyano group and a tri(C.sub.1 to C.sub.3 alkyl)silyl
group.} or the substituted pyrazolyloxy group (The substituent is a
benzoyl group substituted by two chlorine atoms, and two C.sub.1 to
C.sub.3 alkyl groups.),
more preferably a chlorine atom, a bromine atom, trifluoromethyl
group or a cyano group,
still further preferably a chlorine atom or a bromine atom,
particularly preferably a chlorine atom.
(b) In the present invention, R.sup.2 is preferably a hydrogen
atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine
atom, a C.sub.1 to C.sub.3 alkyl group, a (C.sub.1 to C.sub.3
alkoxy)C.sub.1 to C.sub.3 alkyl group, a benzoyl group which may be
substituted {The substituent is the same or different 1 to 2
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl
group, a C.sub.1 to C.sub.3 haloalkyl group (The halogen atom is
the same or different 1 to 3 halogen atom(s) selected from the
group consisting of a fluorine atom, a chlorine atom and a bromine
atom.), a cyclopropyl group, a cyano group and a tri(C.sub.1 to
C.sub.3 alkyl)silyl group.}, a C.sub.2 to C.sub.4 alkoxycarbonyl
group, a phenoxy group which may be substituted {The substituent is
the same or different 1 to 2 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.3 alkyl group, a C.sub.1 to C.sub.3 haloalkyl
group (The halogen atom is the same or different 1 to 3 halogen
atom(s) selected from the group consisting of a fluorine atom, a
chlorine atom and a bromine atom.), a cyclopropyl group, a cyano
group and a tri(C.sub.1 to C.sub.3 alkyl)silyl group.}, a
phenylthio group which may be substituted {The substituent is the
same or different 1 to 2 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.3 alkyl group, a C.sub.1 to C.sub.3 haloalkyl
group (The halogen atom is the same or different 1 to 3 halogen
atom(s) selected from the group consisting of a fluorine atom, a
chlorine atom and a bromine atom.), a cyclopropyl group, a cyano
group and a tri(C.sub.1 to C.sub.3 alkyl)silyl group.} or a
tri(C.sub.1 to C.sub.3 alkyl)silyl group,
more preferably a hydrogen atom, a fluorine atom, a chlorine atom,
a bromine atom, an iodine atom, a methyl group, an ethoxycarbonyl
group or a trimethylsilyl group,
still further preferably a hydrogen atom.
(c) In the present invention, R.sup.3, R.sup.4, R.sup.5, R.sup.6
and R.sup.7 each independently represent preferably a hydrogen
atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine
atom, a C.sub.1 to C.sub.4 alkyl group which may be substituted
(The substituent is the same or different 1 to 3 substituent(s)
selected from the group consisting of a fluorine atom, a chlorine
atom and a bromine atom, or a C.sub.3 to C.sub.4 cycloalkyl group,
a C.sub.1 to C.sub.3 alkylthio group or a C.sub.1 to C.sub.3
alkoxyimino group.), a C.sub.2 to C.sub.3 alkenyl group, a C.sub.2
to C.sub.3 alkynyl group, a C.sub.3 to C.sub.5 cycloalkyl group
which may be substituted (The substituent is the same or different
1 to 3 substituent(s) selected from the group consisting of a
fluorine atom, a chlorine atom, a bromine atom, a C.sub.1 to
C.sub.3 alkyl group, a C.sub.3 to C.sub.4 cycloalkyl group, a cyano
group, a C.sub.1 to C.sub.3 alkoxy group and a C.sub.1 to C.sub.3
alkylthio group.), a C.sub.6 to C.sub.7 bicycloalkyl group, a cyano
group, a C.sub.2 to C.sub.4 alkylcarbonyl group, a C.sub.2 to
C.sub.4 alkoxycarbonyl group, a phenyl group which may be
substituted {The substituent is a fluorine atom, a chlorine atom, a
bromine atom, a C.sub.1 to C.sub.3 alkyl group or a C.sub.1 to
C.sub.3 haloalkyl group (The halogen atom is the same or different
1 to 3 halogen atom(s) selected from the group consisting of a
fluorine atom, a chlorine atom and a bromine atom.).}, a 5- to
6-membered heterocyclic group which may be substituted {the
heterocycle contains one nitrogen atom, oxygen atom or sulfur atom
in the ring, and may contain further 1 or 2 nitrogen atom(s). The
substituent is the same or different 1 to 2 substituent(s) selected
from the group consisting of a fluorine atom, a chlorine atom, a
bromine atom, a C.sub.1 to C.sub.3 alkyl group and a C.sub.1 to
C.sub.3 haloalkyl group (The halogen atom is the same or different
1 to 3 halogen atom(s) selected from the group consisting of a
fluorine atom, a chlorine atom and a bromine atom.).}, a nitro
group, a C.sub.1 to C.sub.3 alkoxy group, a C.sub.1 to C.sub.3
haloalkoxy group (The halogen atom is the same or different 1 to 3
halogen atom(s) selected from the group consisting of a fluorine
atom, a chlorine atom and a bromine atom.), a phenoxy group which
may be substituted (The substituent is a pyridazinyloxy group
substituted by a substituent(s) selected frome the group consisting
of a fluorine atom, a chlorine atom, a bromine atom a C.sub.1 to
C.sub.3 alkoxy group.) or a C.sub.1 to C.sub.3 alkylthio group, or
R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are a group(s) which
is/are formed by the adjacent two of them with carbon atoms to
which the respective substituents are bonded, and include a group
represented by CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2--,
--CH(CH.sub.3)CH.sub.2CH.sub.2--,
--CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --CH.dbd.CH--CH.dbd.CH--,
--OCH.sub.2CH.sub.2--, --OCH.dbd.CH--, --OCH.dbd.C(CH.sub.3)--,
--SCH.dbd.CH--, --N.dbd.CH--CH.dbd.CH--, --OCH.sub.2O--,
--OCH.sub.2CH.sub.2O--,
##STR00006##
more preferably each independently represent a hydrogen atom, a
fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a
C.sub.1 to C.sub.4 alkyl group which may be substituted (The
substituent is 1 to 3 fluorine atom(s), or a cyclopropyl group.), a
C.sub.3 to C.sub.4 cycloalkyl group which may be substituted (The
substituent is the same 1 to 2 substituent selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.2 alkyl group, a cyclopropyl group and a C.sub.1
to C.sub.2 alkoxy group.), a cyano group, C.sub.2 to C.sub.3
alkoxycarbonyl group, a nitro group, C.sub.1 to C.sub.3 alkoxy
group or trifluoromethoxy group, or, R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 are a group(s) which is/are formed by the
adjacent two of them with carbon atoms to which the respective
substituents are bonded, and include a group represented by
--CH.sub.2CH.sub.2CH.sub.2--, --CH(CH.sub.3)CH.sub.2CH.sub.2--,
--OCH.sub.2CH.sub.2--, --OCH.dbd.CH-- or
##STR00007## provided that R.sup.3 is not a hydrogen atom,
still further preferably each independently represent a hydrogen
atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine
atom, C.sub.1 to C.sub.3 alkyl group, a C.sub.3 to C.sub.4
cycloalkyl group which may be substituted (The substituent is the
same 1 to 2 substituent(s) selected from the group consisting of a
chlorine atom and a C.sub.1 to C.sub.2 alkyl group.), a cyano group
or a C.sub.1 to C.sub.2 alkoxy group, or R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 are a group(s) which is/are formed by the
adjacent two of them with carbon atoms to which the respective
substituents are bonded, and include a group represented by
--CH.sub.2CH.sub.2CH.sub.2-- or --OCH.dbd.CH--, provided that
R.sup.3 is not a hydrogen atom,
particularly preferably each independently represent a hydrogen
atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine
atom, a methyl group, an ethyl group, an isopropyl group, a
cyclopropyl group which may be substituted (The substituents are
two chlorine atoms.) or a methoxy group, or R.sup.3, R.sup.4,
R.sup.5, R.sup.6 and R.sup.7 are a group(s) which is/are formed by
the adjacent two of them with carbon atoms to which the respective
substituents are bonded, and include a group represented by
--CH.sub.2CH.sub.2CH.sub.2--, provided that R.sup.3 is not a
hydrogen atom,
most preferably R.sup.3 is a fluorine atom, a chlorine atom, a
bromine atom, an iodine atom, a methyl group, an ethyl group, an
isopropyl group, a cyclopropyl group or a methoxy group , and
R.sup.7 is a hydrogen atom, a fluorine atom, a chlorine atom, a
bromine atom, an iodine atom, a methyl group, an ethyl group, an
isopropyl group, a cyclopropyl group or methoxy group, and R.sup.4,
R.sup.5 and R.sup.6 each independently represent a hydrogen atom or
a methyl group.
(d) In the present invention, m and n are preferably both 0.
The compound (I) of the present invention is preferably a compound
wherein (1a) R.sup.1 is a hydrogen atom, a fluorine atom, a
chlorine atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl group, a
C.sub.1 to C.sub.3 haloalkyl group (The halogen atom is 1 to 3
fluorine atom(s).), a cyclopropyl group, a C.sub.2 to C.sub.3
alkenyl group, a cyano group, a C.sub.2 to C.sub.4 alkylcarbonyl
group, a di(C.sub.1 to C.sub.3 alkyl)carbamoyl group, a phenyl
group which may be substituted {The substituent is the same or
different 1 to 2 substituent(s) selected from the group consisting
of a fluorine atom, a chlorine atom, a bromine atom, a C.sub.1 to
C.sub.3 alkyl group, a C.sub.1 to C.sub.3 haloalkyl group (The
halogen atom is the same or different 1 to 3 halogen atom(s)
selected from the group consisting of a fluorine atom, a chlorine
atom and a bromine atom.), a cyclopropyl group, a cyano group and a
tri(C.sub.1 to C.sub.3 alkyl)silyl group.}, a furyl group, a
thienyl group, a C.sub.1 to C.sub.3 alkoxy group, a phenoxy group
which may be substituted {The substituent is the same or different
1 to 2 substituent(s) selected from the group consisting of a
fluorine atom, a chlorine atom, a bromine atom, a C.sub.1 to
C.sub.3 alkyl group, a C.sub.1 to C.sub.3 haloalkyl group (The
halogen atom is 1 to 3 fluorine atom(s).), a cyclopropyl group, a
cyano group and a tri(C.sub.1 to C.sub.3 alkyl)silyl group.} or the
substituted pyrazolyloxy group (The substituent is a benzoyl group
substituted by two chlorine atoms and two C.sub.1 to C.sub.3 alkyl
groups.), (1b) R.sup.2 is a hydrogen atom, a fluorine atom, a
chlorine atom, a bromine atom, an iodine atom, a C.sub.1 to C.sub.3
alkyl group, a (C.sub.1 to C.sub.3 alkoxy)C.sub.1 to C.sub.3 alkyl
group, a benzoyl group which may be substituted {The substituent is
the same or different 1 to 2 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.3 alkyl group, a C.sub.1 to C.sub.3 haloalkyl
group (The halogen atom is the same or different 1 to 3 halogen
atom(s) selected from the group consisting of a fluorine atom, a
chlorine atom and a bromine atom.), a cyclopropyl group, a cyano
group and a tri(C.sub.1 to C.sub.3 alkyl)silyl group.}, a C.sub.2
to C.sub.4 alkoxycarbonyl group, a phenoxy group which may be
substituted {The substituent is the same or different 1 to 2
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl
group, a C.sub.1 to C.sub.3 haloalkyl group (The halogen atom is
the same or different 1 to 3 halogen atom(s) selected from the
group consisting of a fluorine atom, a chlorine atom and a bromine
atom.), a cyclopropyl group, a cyano group and a tri(C.sub.1 to
C.sub.3 alkyl)silyl group.}, a phenylthio group which may be
substituted {The substituent is the same or different 1 to 2
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl
group, a C.sub.1 to C.sub.3 haloalkyl group (The halogen atom is
the same or different 1 to 3 halogen atom(s) selected from the
group consisting of a fluorine atom, a chlorine atom and a bromine
atom.), a cyclopropyl group, a cyano group and a tri(C.sub.1 to
C.sub.3 alkyl)silyl group.} or a tri(C.sub.1 to C.sub.3 alkyl)silyl
group, (1c) R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each
independently represent a hydrogen atom, a fluorine atom, a
chlorine atom, a bromine atom, an iodine atom, a C.sub.1 to C.sub.4
alkyl group which may be substituted (The substituent is the same
or different 1 to 3 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom and a bromine atom,
or a C.sub.3 to C.sub.4 cycloalkyl group, a C.sub.1 to C.sub.3
alkylthio group or a C.sub.1 to C.sub.3 alkoxyimino group.), a
C.sub.2 to C.sub.3 alkenyl group, a C.sub.2 to C.sub.3 alkynyl
group, a C.sub.3 to C.sub.5 cycloalkyl group which may be
substituted (The substituent is the same or different 1 to 3
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom, a bromine atom, a C.sub.1 to C.sub.3 alkyl
group, a C.sub.3 to C.sub.4 cycloalkyl group, a cyano group, a
C.sub.1 to C.sub.3 alkoxy group and a C.sub.1 to C.sub.3 alkylthio
group.), a C.sub.6 to C.sub.7 bicycloalkyl group, a cyano group, a
C.sub.2 to C.sub.4 alkylcarbonyl group, a C.sub.2 to C.sub.4
alkoxycarbonyl group, a phenyl group which may be substituted {The
substituent is a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.3 alkyl group or a C.sub.1 to C.sub.3 haloalkyl
group (The halogen atom is the same or different 1 to 3 halogen
atom(s) selected from the group consisting of a fluorine atom, a
chlorine atom and a bromine atom.).}, a 5- to 6-membered
heterocyclic group which may be substituted {the heterocycle
contains one nitrogen atom, oxygen atom or sulfur atom in the ring,
and may contain further 1 or 2 nitrogen atom(s). The substituent is
the same or different 1 to 2 substituent(s) selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.3 alkyl group and a C.sub.1 to C.sub.3 haloalkyl
group (The halogen atom is the same or different 1 to 3 halogen
atom(s) selected from the group consisting of a fluorine atom, a
chlorine atom and a bromine atom.).}, a nitro group, a C.sub.1 to
C.sub.3 alkoxy group, a C.sub.1 to C.sub.3 haloalkoxy group (The
halogen atom is the same or different 1 to 3 halogen atom(s)
selected from the group consisting of a fluorine atom, a chlorine
atom and a bromine atom.), a phenoxy group which may be substituted
(The substituent is a pyridazinyloxy group substituted by a
substituent(s) selected from the group consisting of a fluorine
atom, a chlorine atom, a bromine atom or a C.sub.1 to C.sub.3
alkoxy group.) or C.sub.1 to C.sub.3 alkylthio group, or R.sup.3,
R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are a group(s) which is/are
formed by the adjacent two of them with carbon atoms to which the
respective substituents are bonded, and include a group represented
by --CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2--,
--CH(CH.sub.3) CH.sub.2CH.sub.2--,
--CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, --CH.dbd.CH--CH.dbd.CH--,
--OCH.sub.2CH.sub.2--, --OCH.dbd.CH--, --OCH.dbd.C(CH.sub.3)--,
--SCH.dbd.CH--, --N.dbd.CH--CH.dbd.CH--, --OCH.sub.2O--,
--OCH.sub.2CH.sub.2O--,
##STR00008## (1d) m and n are both 0,
more preferably a compound wherein (2a) R.sup.1 is a chlorine atom,
a bromine atom, a trifluoromethyl group or a cyano group, (2b)
R.sup.2 is a hydrogen atom, a fluorine atom, a chlorine atom, a
bromine atom, an iodine atom, a methyl group, an ethoxycarbonyl
group or a trimethylsilyl group, (2c) R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 each independently represent a hydrogen atom, a
fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a
C.sub.1 to C.sub.4 alkyl group which may be substituted (The
substituent is 1 to 3 fluorine atom(s), or a cyclopropyl group.), a
C.sub.3 to C.sub.4 cycloalkyl group which may be substituted (The
substituent is the same 1 to 2 substituent selected from the group
consisting of a fluorine atom, a chlorine atom, a bromine atom, a
C.sub.1 to C.sub.2 alkyl group, a cyclopropyl group and a C.sub.1
to C.sub.2 alkoxy group.), a cyano group, a C.sub.2 to C.sub.3
alkoxycarbonyl group, a nitro group, a C.sub.1 to C.sub.3 alkoxy
group or a trifluoromethoxy group, or R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 are a group(s) which is/are formed by the
adjacent two of them with carbon atoms to which the respective
substituents are bonded, and include a group represented by
--CH.sub.2CH.sub.2CH.sub.2--, --CH(CH.sub.3)CH.sub.2CR.sub.2--,
--OCH.sub.2CH.sub.2--, --OCH.dbd.CH-- or
##STR00009## provided that R.sup.3 is not a hydrogen atom, (2d) m
and n are both 0,
still further preferably a compound wherein (3a) R.sup.1 is a
chlorine atom or a bromine atom, (3b) R.sup.2 is a hydrogen atom,
(3c) R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each
independently represent a hydrogen atom, a fluorine atom, a
chlorine atom, a bromine atom, an iodine atom, C.sub.1 to C.sub.3
alkyl group, a C.sub.3 to C.sub.4 cycloalkyl group which may be
substituted (The substituent is the same 1 to 2 substituent(s)
selected from the group consisting of a chlorine atom and a C.sub.1
to C.sub.2 alkyl group.), a cyano group or a C.sub.1 to C.sub.2
alkoxy group, or R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are
a group(s) which is/are formed by the adjacent two of them with
carbon atoms to which the respective substituents are bonded, and
include a group represented by --CH.sub.2CH.sub.2CH.sub.2-- or
--OCH.dbd.CH--, provided that R.sup.3 is not a hydrogen atom, (3d)
m and n are both 0,
particularly preferably a compound wherein (4a) R.sup.1 is a
chlorine atom, (4b) R.sup.2is a hydrogen atom, (4c) R.sup.3,
R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each independently represent
a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom,
an iodine atom, a methyl group, an ethyl group, an isopropyl group,
a cyclopropyl group which may be substituted (The substituents are
two chlorine atoms.) or a methoxy group, or R.sup.3, R.sup.4,
R.sup.5, R.sup.6 and R.sup.7 are a group(s) which is/are formed by
the adjacent two of them with carbon atoms to which the respective
substituents are bonded, and include a group represented by
--CH.sub.2CH.sub.2CH.sub.2--, provided that R.sup.3 is not a
hydrogen atom, (4d) m and n are both 0.
Representative compounds of the present invention are exemplified
in the following Table 1, but the present invention is not limited
by these compounds.
In the following, in R.sup.3 to R.sup.7, "H" means that all the
R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are hydrogen atoms,
in R.sup.3 to R.sup.7, "2-Cl" means that R.sup.3 is a chlorine
atom, "Me" represents a methyl group, "Et" represents an ethyl
group, "Pr" represents a propyl group, "iPr" represents an
isopropyl group, "cPr" represents a cyclopropyl group, "Bu"
represents a butyl group, "iBu" represents an isobutyl group,
"nsBu" represents a s-butyl group, "tBu" represents a tert-butyl
group, "cBu" represents a cyclobutyl group, "Pen" represents a
pentyl group, "cPen" represents a cyclopentyl group, "neoPen"
represents a neopentyl group, "Hx" represents a hexyl group, "cHx"
represents a cyclohexyl group, in R.sup.3 to R.sup.7,
"2-CH.sub.2CH.sub.2CH.sub.2-3" means that R.sup.3 and R.sup.4 are a
trimethylene group and form a 5-membered ring together with carbon
atoms to which they are bonded, ".dbd.N--OMe" represents a
methoxyimino group, ".dbd.O" represents a carbonyl group together
with carbon atom(s) to which they are bonded, "SO.sub.2 (Ph-4-Me)"
represents a p-tolylsulfonyl group, "cPr-1-F" represents a
1-fluorocyclopropyl group, "cPr-cis-2-(CH.sub.2).sub.3-cis-3"
represents a group represented by
##STR00010## "C(--CH.sub.2CH.sub.2--)--CH.sub.2CH.sub.2" represents
a group represented by
##STR00011## "CH(CH.sub.2)CH--CH.sub.2" represents a group
represented by
##STR00012## "CH(OCH.sub.2).sub.2" represents a group represented
by
##STR00013## "Fur" represents a furyl group, "Thi" represents a
thienyl group, "Pyr" represents a pyridyl group, "Azr" represents a
aziridinyl group, "Pyrd" represents a pyrrolidinyl group, "Pyrr"
represents a pyrrolyl group, "Pyza" represents a pyrazolyl group,
"Thiz" represents a thiazolyl group, "Pyzn" represents a
pyridazinyl group, "Np" represents a naphthyl group, "1-Ad"
represents a 1-adamantyl group, "Ioxa" represents an isoxazolyl
group, "Tdia" represents a 1,2,3-thiadiazolyl group, "Bfur"
represents a 1-benzofuranyl group, "Bthi" represents a
1-benzothienyl group, "Bthia" represents a 1,3-benzothiazolyl
group, "Boxaz" represents a 1,3-benzodioxolyl group, "Iqu"
represents an isquinolyl group, "Azet" represents an azetidinyl
group, "Ppri" represents a piperidyl group,
"1-Ppri-4-OCH.sub.2CH.sub.2O-4" represents a group represented by
the formula:
##STR00014## "Ppra" represents a piperadinyl group, "Morp"
represents a morpholinyl group, "Tmor" represents a thiomorpholinyl
group, "Carb" represents a carbazolyl group, "Pthia" represents a
phenothiazinyl group, "Thpy" represents a tetrahydro-2H-pyranyl
group, "Q.sup.1" represents an oxiranyl group, "Q.sup.2" represents
a benzoxazolyl group, "Q.sup.3" represents a benzothiazolyl group,
"Q.sup.4" represents a fluorenyl group, "Q.sup.5" represents a
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl group,
"Q.sup.6" represents a 6-chloro-3-(2-methylphenoxy)-4-pyridazinyl
group, "Q.sup.7" represents a
6-chloro-3-(2-isopropylphenoxy)-4-pyridazinyl group, "Q.sup.8"
represents a 6-chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl group,
"Q.sup.9" represents a
6-chloro-3-(2,3-dihydro-1H-inden-4-yloxy)-4-pyridazinyl group,
"Q.sup.10" represents a
6-chloro-3-(2,6-dimethylphenoxy)-4-pyridazinyl group, "Q.sup.11"
represents a
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl group,
"Q.sup.l2" represents a
4-[2-chloro-3-(methoxycarbonyl)-4-(methylsulfonyl)benzoyl]-1-ethyl-1H-pyr-
azol-5-yl group, "Q.sup.13" represents a
4-(2,4-dichloro-3-methylbenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl
group, "Q.sup.14" represents a
2-[2-chloro-4-(methylsulfonyl)benzoyl]-3-oxo-1-cyclohexen-1-yl
group, "Q.sup.15" represents a
2-[4-(methylsulfonyl)-2-nitrobenzoyl]-3-oxo-1-cyclohexen-1-yl
group, "Q.sup.16" represents a
2-cyano-1-cyclopropyl-3-[2-(methylsulfonyl)-4-(trifluoromethyl)phenyl]-3--
oxo-1-propenyl group, "Q.sup.17" represents a
3-[4-chloro-2-(methylsulfonyl)phenyl]-2-cyano-1-cyclopropyl-3-oxo-1-prope-
nyl group, and "Q.sup.18" represents a 3,4-dihydro-2
(1H)-isoquinolinyl group, respectively.
TABLE-US-00001 TABLE 1 ##STR00015## Compound No. R.sup.1 R.sup.2 X
R.sup.3 to R.sup.7 m n 1 H H H H 0 0 2 H H H 2-Cl 0 0 3 H H H 2-Br
0 0 4 H H H 2-I 0 0 5 H H H 2-Me 0 0 6 H H H 2-iPr 0 0 7 H H H
2-cPr 0 0 8 H H H 2-cBu 0 0 9 H H H 2-CH.sub.2CH.sub.2CH.sub.2-3 0
0 10 H H H 2-cPr,5-Me 0 0 11 H H H 2-OMe,5-Me 0 0 12 H H H 2-F,
6-iPr 0 0 13 H H H 2-Cl, 6-cPr 0 0 14 H H H 2-Br, 6-Me 0 0 15 H H H
2-I, 6-Me 0 0 16 H H H 2, 6-Me.sub.2 0 0 17 H H H 2-Me, 6-Et 0 0 18
H H H 2-Me, 6-cPr 0 0 19 H H H 2, 6-cPr.sub.2 0 0 20 H H H 2-cPr,
3,5-Me.sub.2 0 0 21 H H H 2-cPr, 5,6-Me.sub.2 0 0 22 H H SO.sub.2
(Ph-4-Me) 2-Cl 0 0 23 H H SO.sub.2 (Ph-4-Me) 2-Br 0 0 24 H H
SO.sub.2 (Ph-4-Me) 2-I 0 0 25 H H SO.sub.2 (Ph-4-Me) 2-Me 0 0 26 H
H SO.sub.2 (Ph-4-Me) 2-iPr 0 0 27 H H SO.sub.2 (Ph-4-Me) 2-cPr 0 0
28 H H SO.sub.2 (Ph-4-Me) 2-cBu 0 0 29 H H SO.sub.2 (Ph-4-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 30 H H SO.sub.2 (Ph-4-Me) 2-cPr,
5-Me 0 0 31 H H SO.sub.2 (Ph-4-Me) 2-OMe, 5-Me 0 0 32 H H SO.sub.2
(Ph-4-Me) 2-F, 6-iPr 0 0 33 H H SO.sub.2 (Ph-4-Me) 2-Cl, 6-cPr 0 0
34 H H SO.sub.2 (Ph-4-Me) 2-Br, 6-Me 0 0 35 H H SO.sub.2 (Ph-4-Me)
2-I, 6-Me 0 0 36 H H SO.sub.2 (Ph-4-Me) 2, 6-Me.sub.2 0 0 37 H H
SO.sub.2 (Ph-4-Me) 2-Me, 6-Et 0 0 38 H H SO.sub.2 (Ph-4-Me) 2-Me,
6-cPr 0 0 39 H H SO.sub.2 (Ph-4-Me) 2, 6-cPr.sub.2 0 0 40 H H
SO.sub.2 (Ph-4-Me) 2-cPr, 3,5-Me.sub.2 0 0 41 H H SO.sub.2
(Ph-4-Me) 2-cPr, 5, 6-Me.sub.2 0 0 42 H Cl H 2-Cl 0 0 43 H Cl H
2-Br 0 0 44 H Cl H 2-I 0 0 45 H Cl H 2-Me 0 0 46 H Cl H 2-Et 0 0 47
H Cl H 2-iPr 0 0 48 H Cl H 2-cPr 0 0 49 H Cl H 2-cBu 0 0 50 H Cl H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 51 H Cl H 2-cPr, 5-Me 0 0 52 H Cl
H 2-OMe, 5-Me 0 0 53 H Cl H 2-F, 6-iPr 0 0 54 H Cl H 2-Cl, 6-cPr 0
0 55 H Cl H 2-Br, 6-Me 0 0 56 H Cl H 2-I, 6-Me 0 0 57 H Cl H 2,
6-Me.sub.2 0 0 58 H Cl H 2-Me, 6-Et 0 0 59 H Cl H 2-Me, 6-cPr 0 0
60 H Cl H 2,6-cPr.sub.2 0 0 61 H Cl H 2-cPr, 3,5-Me.sub.2 0 0 62 H
Cl H 2-cPr, 5, 6-Me.sub.2 0 0 63 H Cl SO.sub.2 (Ph-4-Me) 2-Cl 0 0
64 H Cl SO.sub.2 (Ph-4-Me) 2-Br 0 0 65 H Cl SO.sub.2 (Ph-4-Me) 2-I
0 0 66 H Cl SO.sub.2 (Ph-4-Me) 2-Me 0 0 67 H Cl SO.sub.2 (Ph-4-Me)
2-iPr 0 0 68 H Cl SO.sub.2 (Ph-4-Me) 2-cPr 0 0 69 H Cl SO.sub.2
(Ph-4-Me) 2-cBu 0 0 70 H Cl SO.sub.2 (Ph-4-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 71 H Cl SO.sub.2 (Ph-4-Me) 2-cPr,
5-Me 0 0 72 H Cl SO.sub.2 (Ph-4-Me) 2-OMe, 5-Me 0 0 73 H Cl
SO.sub.2 (Ph-4-Me) 2-F, 6-iPr 0 0 74 H Cl SO.sub.2 (Ph-4-Me) 2-Cl,
6-cPr 0 0 75 H Cl SO.sub.2 (Ph-4-Me) 2-Br, 6-Me 0 0 76 H Cl
SO.sub.2 (Ph-4-Me) 2-I, 6-Me 0 0 77 H Cl SO.sub.2 (Ph-4-Me)
2,6-Me.sub.2 0 0 78 H Cl SO.sub.2 (Ph-4-Me) 2-Me, 6-Et 0 0 79 H Cl
SO.sub.2 (Ph-4-Me) 2-Me, 6-cPr 0 0 80 H Cl SO.sub.2 (Ph-4-Me)
2,6-cPr.sub.2 0 0 81 H Cl SO.sub.2 (Ph-4-Me) 2-cPr, 3,5-Me.sub.2 0
0 82 H Cl SO.sub.2 (Ph-4-Me) 2-cPr, 5, 6-Me.sub.2 0 0 83 H
SiMe.sub.3 H 2-Cl 0 0 84 H SiMe.sub.3 H 2-Br 0 0 85 H SiMe.sub.3 H
2-I 0 0 86 H SiMe.sub.3 H 2-Me 0 0 87 H SiMe.sub.3 H 2-iPr 0 0 88 H
SiMe.sub.3 H 2-cPr 0 0 89 H SiMe.sub.3 H 2-cBu 0 0 90 H SiMe.sub.3
H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 91 H SiMe.sub.3 H 2-cPr, 5-Me 0
0 92 H SiMe.sub.3 H 2-OMe, 5-Me 0 0 93 H SiMe.sub.3 H 2-F, 6-iPr 0
0 94 H SiMe.sub.3 H 2-Cl, 6-cPr 0 0 95 H SiMe.sub.3 H 2-Br, 6-Me 0
0 96 H SiMe.sub.3 H 2-I, 6-Me 0 0 97 H SiMe.sub.3 H 2,6-Me.sub.2 0
0 98 H SiMe.sub.3 H 2-Me, 6-Et 0 0 99 H SiMe.sub.3 H 2-Me, 6-cPr 0
0 100 H SiMe.sub.3 H 2,6-cPr.sub.2 0 0 101 H SiMe.sub.3 H 2-cPr,
3,5-Me.sub.2 0 0 102 H SiMe.sub.3 H 2-cPr, 5,6-Me.sub.2 0 0 103 H
SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-Cl 0 0 104 H SiMe.sub.3 SO.sub.2
(Ph-4-Me) 2-Br 0 0 105 H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-I 0 0 106
H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-Me 0 0 107 H SiMe.sub.3 SO.sub.2
(Ph-4-Me) 2-iPr 0 0 108 H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-cPr 0 0
109 H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-cBu 0 0 110 H SiMe.sub.3
SO.sub.2 (Ph-4-Me) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 111 H
SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-cPr, 5-Me 0 0 112 H SiMe.sub.3
SO.sub.2 (Ph-4-Me) 2-OMe, 5-Me 0 0 113 H SiMe.sub.3 SO.sub.2
(Ph-4-Me) 2-F, 6-iPr 0 0 114 H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-Cl,
6-cPr 0 0 115 H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-Br, 6-Me 0 0 116 H
SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-I, 6-Me 0 0 117 H SiMe.sub.3
SO.sub.2 (Ph-4-Me) 2,6-Me.sub.2 0 0 118 H SiMe.sub.3 SO.sub.2
(Ph-4-Me) 2-Me, 6-Et 0 0 119 H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-Me,
6-cPr 0 0 120 H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2,6-cPr.sub.2 0 0 121
H SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-cPr, 3,5-Me.sub.2 0 0 122 H
SiMe.sub.3 SO.sub.2 (Ph-4-Me) 2-cPr, 5,6-Me.sub.2 0 0 123 Cl H H H
0 0 124 Cl H H 2-F 0 0 125 Cl H H 2-Cl 0 0 126 Cl H H 2-Br 0 0 127
Cl H H 2-I 0 0 128 Cl H H 2-Me 0 0 129 Cl H H 2-Me 1 0 130 Cl H H
2-Et 0 0 131 Cl H H 2-Pr 0 0 132 Cl H H 2-iPr 0 0 133 Cl H H 2-Bu 0
0 134 Cl H H 2-iBu 0 0 135 Cl H H 2-sBu 0 0 136 Cl H H 2-tBu 0 0
137 Cl H H 2-Pen 0 0 138 Cl H H 2-Hx 0 0 139 Cl H H 2-cPr 0 0 140
Cl H H 2-(cPr-1-F) 0 0 141 Cl H H 2-(cPr-1-Cl) 0 0 142 Cl H H
2-(cPr-1-Br) 0 0 143 Cl H H 2-(cPr-1-I) 0 0 144 Cl H H 2-(cPr-1-Me)
0 0 145 Cl H H 2-(cPr-1-Et) 0 0 146 Cl H H 2-(cPr-1-Pr) 0 0 147 Cl
H H 2-(cPr-1-iPr) 0 0 148 Cl H H 2-(cPr-1-Bu) 0 0 149 Cl H H
2-(cPr-1-tBu) 0 0 150 Cl H H 2-(cPr-1-Hx) 0 0 151 Cl H H
2-(cPr-1-cPr) 0 0 152 Cl H H 2-(cPr-1-cBu) 0 0 153 Cl H H
2-(cPr-1-cPen) 0 0 154 Cl H H 2-(cPr-1-CH.sub.2F) 0 0 155 Cl H H
2-(cPr-1-CH.sub.2Cl) 0 0 156 Cl H H 2-(cPr-1-CH.sub.2Br) 0 0 157 Cl
H H 2-(cPr-1-CHF.sub.2) 0 0 158 Cl H H 2-(cPr-1-CF.sub.3) 0 0 159
Cl H H 2-(cPr-1-CCl.sub.3) 0 0 160 Cl H H
2-(cPr-1-CH.sub.2CF.sub.3) 0 0 161 Cl H H
2-(cPr-1-CH.sub.2CCl.sub.3) 0 0 162 Cl H H
2-(cPr-1-CH.dbd.CH.sub.2) 0 0 163 Cl H H 2-(cPr-1-CH.sub.2OMe) 0 0
164 Cl H H 2-(cPr-1-CH.sub.2OEt) 0 0 165 Cl H H
2-(cPr-1-CH.sub.2OiPr) 0 0 166 Cl H H 2-(cPr-1-CH.sub.2SMe) 0 0 167
Cl H H 2-(cPr-1-CH.sub.2SEt) 0 0 168 Cl H H 2-(cPr-1-CH.sub.2S-iPr)
0 0 169 Cl H H 2-(cPr-1-CH.sub.2SOMe) 0 0 170 Cl H H
2-(cPr-1-CH.sub.2SOEt) 0 0 171 Cl H H 2-(cPr-1-CH.sub.2SO.sub.2Me)
0 0 172 Cl H H 2-(cPr-1-CH.sub.2SO.sub.2Et) 0 0 173 Cl H H
2-(cPr-1-CN) 0 0 174 Cl H H 2-{cPr-1-C(.dbd.NOMe)Me} 0 0 175 Cl H H
2-(cPr-1-COMe) 0 0 176 Cl H H 2-(cPr-1-COEt) 0 0 177 Cl H H
2-(cPr-1-COPh) 0 0 178 Cl H H 2-(cPr-1-CO.sub.2H) 0 0 179 Cl H H
2-(cPr-1-CO.sub.2Me) 0 0 180 Cl H H 2-(cPr-1-CO.sub.2Et) 0 0 181 Cl
H H 2-(cPr-1-CONH.sub.2) 0 0 182 Cl H H 2-(cPr-1-CONMe.sub.2) 0 0
183 Cl H H 2-(cPr-1-CONEt.sub.2) 0 0 184 Cl H H 2-(cPr-1-Ph) 0 0
185 Cl H H 2-{cPr-1-(Ph-2-F)} 0 0 186 Cl H H 2-{cPr-1-(Ph-2-Cl)} 0
0 187 Cl H H 2-{cPr-1-(Ph-2-Me)} 0 0 188 Cl H H 2-{cPr-1-(Ph-4-Cl)}
0 0 189 Cl H H 2-{cPr-1-(Ph-4-Me)} 0 0 190 Cl H H 2-{cPr-1-(2-Fur)}
0 0 191 Cl H H 2-{cPr-1-(2-Thi)} 0 0 192 Cl H H 2-{cPr-1-(2-Pyr)} 0
0 193 Cl H H 2-(cPr-1-NH.sub.2) 0 0 194 Cl H H 2-(cPr-1-NHMe) 0 0
195 Cl H H 2-(cPr-1-NMe.sub.2) 0 0 196 Cl H H 2-(cPr-1-NHCOMe) 0 0
197 Cl H H 2-(cPr-1-NHCO.sub.2Me) 0 0 198 Cl H H
2-(cPr-1-NHCONMe.sub.2) 0 0 199 Cl H H 2-(cPr-1-NHSO.sub.2Me) 0 0
200 Cl H H 2-(cPr-1-NO.sub.2) 0 0 201 Cl H H 2-(cPr-1-OH) 0 0 202
Cl H H 2-(cPr-1-OMe) 0 0 203 Cl H H 2-(cPr-1-OEt) 0 0 204 Cl H H
2-(cPr-1-OCF.sub.3) 0 0 205 Cl H H 2-(cPr-1-OPh) 0 0 206 Cl H H
2-(cPr-1-SMe) 0 0 207 Cl H H 2-(cPr-1-SEt) 0 0 208 Cl H H
2-(cPr-1-SPh) 0 0 209 Cl H H 2-(cPr-1-SOMe) 0 0 210 Cl H H
2-(cPr-1-SOEt) 0 0 211 Cl H H 2-(cPr-1-SO.sub.2Me) 0 0 212 Cl H H
2-(cPr-1-SO.sub.2Et) 0 0 213 Cl H H 2-(cPr-2-F) 0 0 214 Cl H H
2-(cPr-2-Cl) 0 0 215 Cl H H 2-(cPr-2-Br) 0 0 216 Cl H H 2-(cPr-2-I)
0 0 217 Cl H H 2-(cPr-2-Me) 0 0 218 Cl H H 2-(cPr-2-Et) 0 0 219 Cl
H H 2-(cPr-2-Pr) 0 0 220 Cl H H 2-(cPr-2-iPr) 0 0 221 Cl H H
2-(cPr-2-Bu) 0 0 222 Cl H H 2-(cPr-2-tBu) 0 0 223 Cl H H
2-(cPr-2-Hx) 0 0 224 Cl H H 2-(cPr-2-cPr) 0 0 225 Cl H H
2-(cPr-2-CF.sub.3) 0 0 226 Cl H H 2-(cPr-2-CN) 0 0 227 Cl H H
2-(cPr-2-CH.sub.2OMe) 0 0 228 Cl H H 2-(cPr-2-CH.sub.2OEt) 0 0 229
Cl H H 2-{cPr-2-C(.dbd.NOMe)Me} 0 0 230 Cl H H 2-(cPr-2-COMe) 0 0
231 Cl H H 2-(cPr-2-COEt) 0 0 232 Cl H H 2-(cPr-2-COPh) 0 0 233 Cl
H H 2-(cPr-2-CO.sub.2H) 0 0 234 Cl H H 2-(cPr-2-CO.sub.2Me) 0 0 235
Cl H H 2-(cPr-2-CO.sub.2Et) 0 0 236 Cl H H 2-(cPr-2-CONH.sub.2) 0 0
237 Cl H H 2-(cPr-2-CONMe.sub.2) 0 0 238 Cl H H
2-(cPr-2-CONEt.sub.2) 0 0 239 Cl H H 2-(cPr-2-NH.sub.2) 0 0 240 Cl
H H 2-(cPr-2-NHMe) 0 0 241 Cl H H 2-(cPr-2-NMe.sub.2) 0 0 242 Cl H
H 2-(cPr-2-NHCOMe) 0 0 243 Cl H H 2-(cPr-2-NHCO.sub.2Me) 0 0
244 Cl H H 2-(cPr-2-NHCONMe.sub.2) 0 0 245 Cl H H
2-(cPr-2-NHSO.sub.2Me) 0 0 246 Cl H H 2-(cPr-2-NO.sub.2) 0 0 247 Cl
H H 2-(cPr-2-OH) 0 0 248 Cl H H 2-(cPr-2-OMe) 0 0 249 Cl H H
2-(cPr-2-OEt) 0 0 250 Cl H H 2-(cPr-2-OCF.sub.3) 0 0 251 Cl H H
2-(cPr-2-OPh) 0 0 252 Cl H H 2-(cPr-2-SMe) 0 0 253 Cl H H
2-(cPr-2-SEt) 0 0 254 Cl H H 2-(cPr-2-SPh) 0 0 255 Cl H H
2-(cPr-2-SOMe) 0 0 256 Cl H H 2-(cPr-2-SOEt) 0 0 257 Cl H H
2-(cPr-2-SO.sub.2Me) 0 0 258 Cl H H 2-(cPr-2-SO.sub.2Et) 0 0 259 Cl
H H 2-(cPr-1,2-Me.sub.2) 0 0 260 Cl H H 2-(cPr-1-Me-2-Et) 0 0 261
Cl H H 2-(cPr-1-Et-2-Me) 0 0 262 Cl H H 2-(cPr-1,2-Et.sub.2) 0 0
263 Cl H H 2-{cPr-1,2-(CN).sub.2} 0 0 264 Cl H H
2-(cPr-2,2-F.sub.2) 0 0 265 Cl H H 2-(cPr-2,2-Cl.sub.2) 0 0 266 Cl
H H 2-(cPr-2,2-Br.sub.2) 0 0 267 Cl H H 2-(cPr-2,2-Me.sub.2) 0 0
268 Cl H H 2-{cPr-2,2-(CN).sub.2} 0 0 269 Cl H H
2-(cPr-2-cis-3-cis-Me.sub.2) 0 0 270 Cl H H
2-(cPr-2-cis-3-trans-Me.sub.2) 0 0 271 Cl H H
2-(cPr-2-trans-3-trans-Me.sub.2) 0 0 272 Cl H H
2-{cPr-cis-2-(CH.sub.2).sub.3-cis-3} 0 0 273 Cl H H
2-{cPr-trans-2-(CH.sub.2).sub.3-trans-3} 0 0 274 Cl H H
2-{cPr-cis-2-(CH.sub.2).sub.4-cis-3} 0 0 275 Cl H H
2-(cPr-trans-2-(CH.sub.2).sub.4-trans-3) 0 0 276 Cl H H
2-{cPr-2,3-(CN).sub.2} 0 0 277 Cl H H 2-(cPr-1,2,2-Me.sub.3) 0 0
278 Cl H H 2-(cPr-1,2,3-Me.sub.3) 0 0 279 Cl H H
2-(cPr-2,2,3-cis-Me.sub.3) 0 0 280 Cl H H
2-(cPr-2,2,3-trans-Me.sub.3) 0 0 281 Cl H H
2-(cPr-1,2,2,3-Me.sub.4) 0 0 282 Cl H H 2-(cPr-2,2,3,3-Me.sub.4) 0
0 283 Cl H H 2-(cPr-1,2,2,3,3-Me5) 0 0 284 Cl H H 2-cBu 0 0 285 Cl
H H 2-(cBu-1-Me) 0 0 286 Cl H H 2-(cBu-1-CH.dbd.CH.sub.2) 0 0 287
Cl H H 2-(cBu-1-CN) 0 0 288 Cl H H 2-(cBu-1-CO.sub.2H) 0 0 289 Cl H
H 2-(cBu-1-COMe) 0 0 290 Cl H H 2-(cBu-1-CO.sub.2Me) 0 0 291 Cl H H
2-(cBu-1-NH.sub.2) 0 0 292 Cl H H 2-cPen 0 0 293 Cl H H 2-cHx 0 0
294 Cl H H 2-CH.sub.2F 0 0 295 Cl H H 2-CH.sub.2Cl 0 0 296 Cl H H
2-CH.sub.2Br 0 0 297 Cl H H 2-CHF.sub.2 0 0 298 Cl H H 2-CHCl.sub.2
0 0 299 Cl H H 2-CHBr.sub.2 0 0 300 Cl H H 2-CF.sub.3 0 0 301 Cl H
H 2-CCl.sub.3 0 0 302 Cl H H 2-CBr.sub.3 0 0 303 Cl H H
2-CH.dbd.CH.sub.2 0 0 304 Cl H H 2-CMe.dbd.CH.sub.2 0 0 305 Cl H H
2-CH.dbd.CHMe 0 0 306 Cl H H 2-CH.dbd.CHCN 0 0 307 Cl H H
2-CH.sub.2CH.dbd.CH.sub.2 0 0 308 Cl H H 2-C CH 0 0 309 Cl H H 2-C
CMe 0 0 310 Cl H H 2-C CSiMe.sub.3 0 0 311 Cl H H 2-CH.sub.2cPr 0 0
312 Cl H H 2-CH.sub.2cBu 0 0 313 Cl H H 2-CH.sub.2cPen 0 0 314 Cl H
H 2-CH.sub.2cHx 0 0 315 Cl H H 2-CH.sub.2Ph 0 0 316 Cl H H
2-CH.sub.2CN 0 0 317 Cl H H 2-CHMeCN 0 0 318 Cl H H 2-CMe.sub.2CN 0
0 319 Cl H H 2-CH.sub.2COMe 0 0 320 Cl H H 2-CH.sub.2CO.sub.2Me 0 0
321 Cl H H 2-CHMeCO.sub.2Me 0 0 322 Cl H H 2-CH.sub.2CO.sub.2Et 0 0
323 Cl H H 2-CHMeCO.sub.2Et 0 0 324 Cl H H 2-CH.sub.2OMe 0 0 325 Cl
H H 2-CH.sub.2OEt 0 0 326 Cl H H 2-CH.sub.2SMe 0 0 327 Cl H H
2-CH.sub.2SO.sub.2Et 0 0 328 Cl H H 2-CH(OMe).sub.2 0 0 329 Cl H H
2-CH(OCH.sub.2).sub.2 0 0 330 Cl H H 2-CN 0 0 331 Cl H H
2-CH.dbd.NOH 0 0 332 Cl H H 2-CH.dbd.NOMe 0 0 333 Cl H H
2-CMe.dbd.NOH 0 0 334 Cl H H 2-CMe.dbd.NOMe 0 0 335 Cl H H 2-CHO 0
0 336 Cl H H 2-COMe 0 0 337 Cl H H 2-COtBu 0 0 338 Cl H H 2-COPh 0
0 339 Cl H H 2-CO.sub.2Me 0 0 340 Cl H H 2-CO.sub.2tBu 0 0 341 Cl H
H 2-CO.sub.2H 0 0 342 Cl H H 2-CONH.sub.2 0 0 343 Cl H H
2-CONMe.sub.2 0 0 344 Cl H H 2-Ph 0 0 345 Cl H H 2-(Ph-2-Cl) 0 0
346 Cl H H 2-(Ph-2-Me) 0 0 347 Cl H H 2-(Ph-2-CF.sub.3) 0 0 348 Cl
H H 2-(Ph-3-CF.sub.3) 0 0 (Isomer A) 349 Cl H H 2-(Ph-3-CF.sub.3) 0
0 (Isomer B) 350 Cl H H 2-(1-Azr) 0 0 351 Cl H H 2-(2-Azr) 0 0 352
Cl H H 2-{2-Azr-1-SO.sub.2--(Ph-4-Me)} 0 0 353 Cl H H
2-(2-Q.sup.1-2-Me) 0 0 354 Cl H H 2-(2-Q.sup.1-3-Me) 0 0 355 Cl H H
2-(1-Pyrd) 0 0 356 Cl H H 2-(1-Pyrr) 0 0 357 Cl H H 2-(2-Fur) 0 0
358 Cl H H 2-(3-Fur) 0 0 359 Cl H H 2-(2-Thi) 0 0 360 Cl H H
2-(2-Thi-3-Cl) 0 0 361 Cl H H 2-(3-Thi) 0 0 362 Cl H H 2-(1-Pyza) 0
0 363 Cl H H 2-(1-Pyza-3-Me) 0 0 364 Cl H H 2-(1-Pyza-3,5-Me.sub.2)
0 0 365 Cl H H 2-(1-Pyza-3-CF.sub.3) 0 0 366 Cl H H
2-(1-Pyza-4-CF.sub.3) 0 0 367 Cl H H 2-(1-Pyza-5-CF.sub.3) 0 0 368
Cl H H 2-(3-Pyza-1-SO.sub.2NMe.sub.2) 0 0 369 Cl H H
2-(5-Pyza-1-SO.sub.2NMe.sub.2) 0 0 370 Cl H H 2-(2-Thiz-4-Me) 0 0
371 Cl H H 2-(2-Pyr) 0 0 372 Cl H H 2-(3-Pyr) 0 0 373 Cl H H
2-(4-Pyr) 0 0 374 Cl H H 2-(1-Pyr-2-OH) 0 0 375 Cl H H
2-(2-Q.sup.2) 0 0 376 Cl H H 2-(2-Q.sup.3) 0 0 377 Cl H H
2-NH.sub.2 0 0 378 Cl H H 2-NHMe 0 0 379 Cl H H 2-NMe.sub.2 0 0 380
Cl H H 2-NHCOMe 0 0 381 Cl H H 2-NHCO.sub.2Me 0 0 382 Cl H H
2-NHCONMe.sub.2 0 0 383 Cl H H 2-NO.sub.2 0 0 384 Cl H H 2-OH 0 0
385 Cl H H 2-OMe 0 0 386 Cl H H 2-OEt 0 0 387 Cl H H 2-OiPr 0 0 388
Cl H H 2-OtBu 0 0 389 Cl H H 2-OCH.sub.2F 0 0 390 Cl H H
2-OCHF.sub.2 0 0 391 Cl H H 2-OCF.sub.3 0 0 392 Cl H H
2-OCH.sub.2CF.sub.3 0 0 393 Cl H H 2-OCH.sub.2CCl.sub.3 0 0 394 Cl
H H 2-OCH.sub.2OMe 0 0 395 Cl H H 2-OCH.sub.2OEt 0 0 396 Cl H H
2-OCH.sub.2CH.sub.2OMe 0 0 397 Cl H H 2-OCH.sub.2CH.sub.2OEt 0 0
398 Cl H H 2-OPh 0 0 399 Cl H H 2-O(Ph-2-OH) 0 0 400 Cl H H
2-O{Ph-2-O(3-Pyzn-6-Cl-4-OEt)} 0 0 401 Cl H H 2-SMe 0 0 402 Cl H H
2-SEt 0 0 403 Cl H H 2-S-iPr 0 0 404 Cl H H 2-SOMe 0 0 405 Cl H H
2-SOEt 0 0 406 Cl H H 2-SO.sub.2Me 0 0 407 Cl H H 2-SO.sub.2Et 0 0
408 Cl H H 2-SiMe.sub.3 0 0 409 Cl H H 3-F 0 0 410 Cl H H 3-Cl 0 0
411 Cl H H 3-Br 0 0 412 Cl H H 3-I 0 0 413 Cl H H 3-Me 0 0 414 Cl H
H 3-Et 0 0 415 Cl H H 3-iPr 0 0 416 Cl H H 3-tBu 0 0 417 Cl H H
3-cPr 0 0 418 Cl H H 3-CF.sub.3 0 0 419 Cl H H 3-(2-Fur) 0 0 420 Cl
H H 3-CN 0 0 421 Cl H H 3-CHO 0 0 422 Cl H H 3-COMe 0 0 423 Cl H H
3-CO.sub.2Me 0 0 424 Cl H H 3-NO.sub.2 0 0 425 Cl H H 3-OMe 0 0 426
Cl H H 4-F 0 0 427 Cl H H 4-Cl 0 0 428 Cl H H 4-Br 0 0 429 Cl H H
4-I 0 0 430 Cl H H 4-Me 0 0 431 Cl H H 4-Et 0 0 432 Cl H H 4-iPr 0
0 433 Cl H H 4-tBu 0 0 434 Cl H H 4-cPr 0 0 435 Cl H H 4-OMe 0 0
436 Cl H H 4-SiMe.sub.3 0 0 437 Cl H H 2,3-F.sub.2 0 0 438 Cl H H
2-F, 3-Cl 0 0 439 Cl H H 2-F, 3-Br 0 0 440 Cl H H 2-F, 3-Me 0 0 441
Cl H H 2-F, 3-CF.sub.3 0 0 442 Cl H H 2-Cl, 3-F 0 0 443 Cl H H
2,3-Cl.sub.2 0 0 444 Cl H H 2-Cl, 3-Br 0 0 445 Cl H H 2-Cl, 3-Me 0
0 446 Cl H H 2-Cl, 3-CF.sub.3 0 0 447 Cl H H 2-Cl, 3-OMe 0 0 448 Cl
H H 2-Br, 3-F 0 0 449 Cl H H 2-Br, 3-Cl 0 0 450 Cl H H 2-Br, 3-Me 0
0 451 Cl H H 2-Br, 3-CF.sub.3 0 0 452 Cl H H 2-Br, 3-OMe 0 0 453 Cl
H H 2-Me, 3-F 0 0 454 Cl H H 2-Me, 3-Cl 0 0 455 Cl H H 2-Me, 3-Br 0
0 456 Cl H H 2,3-Me.sub.2 0 0 457 Cl H H 2-Me, 3-CF.sub.3 0 0 458
Cl H H 2-Me, 3-NO.sub.2 0 0 459 Cl H H 2-Me, 3-OMe 0 0 460 Cl H H
2-Me, 3-O(3-Pyzn-6-Cl-4-OH) 0 0 461 Cl H H 2-Et, 3-F 0 0 462 Cl H H
2-Et, 3-Cl 0 0 463 Cl H H 2-Et, 3-Br 0 0 464 Cl H H 2-Et, 3-Me 0 0
465 Cl H H 2-iPr, 3-F 0 0 466 Cl H H 2-iPr, 3-Cl 0 0 467 Cl H H
2-iPr, 3-Me 0 0 468 Cl H H 2-iPr, 3-Et 0 0 469 Cl H H 2-cPr, 3-F 0
0 470 Cl H H 2-cPr, 3-Cl 0 0 471 Cl H H 2-cPr, 3-Br 0 0 472 Cl H H
2-cPr, 3-Me 0 0 473 Cl H H 2-cPr, 3-Et 0 0 474 Cl H H 2-cPr,
3-CF.sub.3 0 0 475 Cl H H 2-cPr, 3-CN 0 0 476 Cl H H 2-cPr,
3-CO.sub.2Me 0 0 477 Cl H H 2-cPr, 3-NO.sub.2 0 0 478 Cl H H 2-cPr,
3-OMe 0 0 479 Cl H H 2-cBu, 3-F 0 0 480 Cl H H 2-cBu, 3-Cl 0 0 481
Cl H H 2-cBu, 3-Br 0 0 482 Cl H H 2-cBu, 3-Me 0 0 483 Cl H H
2-CF.sub.3, 3-F 0 0 484 Cl H H 2-CF.sub.3, 3-Cl 0 0 485 Cl H H
2-CF.sub.3, 3-Br 0 0 486 Cl H H 2-CF.sub.3, 3-Me 0 0 487 Cl H H
2-CN, 3-F 0 0 488 Cl H H 2-CN, 3-Cl 0 0 489 Cl H H 2-CN, 3-Br 0 0
490 Cl H H 2-CN, 3-Me 0 0 491 Cl H H 2-CO.sub.2Me, 3-F 0 0 492 Cl H
H 2-CO.sub.2Me, 3-Cl 0 0
493 Cl H H 2-CO.sub.2Me, 3-Br 0 0 494 Cl H H 2-CO.sub.2Me, 3-Me 0 0
495 Cl H H 2-NO.sub.2, 3-F 0 0 496 Cl H H 2-NO.sub.2, 3-Cl 0 0 497
Cl H H 2-NO.sub.2, 3-Br 0 0 498 Cl H H 2-NO.sub.2, 3-Me 0 0 499 Cl
H H 2-OMe, 3-F 0 0 500 Cl H H 2-OMe, 3-Cl 0 0 501 Cl H H 2-OMe,
3-Br 0 0 502 Cl H H 2-OMe, 3-Me 0 0 503 Cl H H 2-OMe, 3-OMe 0 0 504
Cl H H 2-CH.sub.2-3 0 0 505 Cl H H 2-CH.sub.2CH.sub.2-3 0 0 506 Cl
H H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 507 Cl H H
2-CHMeCH.sub.2CH.sub.2-3 0 0 508 Cl H H 2-CH(OMe)CH.sub.2CH.sub.2-3
0 0 509 Cl H H 2-CH.sub.2CHMeCH.sub.2-3 0 0 510 Cl H H
2-CH.sub.2CH.sub.2CHMe-3 0 0 511 Cl H H
2-CMe.sub.2CH.sub.2CH.sub.2-3 0 0 512 Cl H H
2-C(OMe).sub.2CH.sub.2CH.sub.2-3 0 0 513 Cl H H
2-CH.sub.2CMe.sub.2CH.sub.2-3 0 0 514 Cl H H
2-C(--CH.sub.2CH.sub.2--)--CH.sub.2CH.sub.2-3 0 0 515 Cl H H
2-CH(CH.sub.2)CH--CH.sub.2-3 0 0 516 Cl H H
2-CH.sub.2--CH(CH.sub.2)CH-3 0 0 517 Cl H H
2-C(.dbd.O)CH.sub.2CH.sub.2-3 0 0 518 Cl H H
2-CH.sub.2C(.dbd.O)CH.sub.2-3 0 0 519 Cl H H
2-CH.sub.2CH.sub.2C(.dbd.O)-3 0 0 520 Cl H H
2-C(.dbd.NOMe)CH.sub.2CH.sub.2-3 0 0 521 Cl H H
2-CH.sub.2CH.sub.2CH.sub.2CH.sub.2-3 0 0 522 Cl H H
2-CHMeCH.sub.2CH.sub.2CH.sub.2-3 0 0 523 Cl H H
2-CMe.sub.2CH.sub.2CH.sub.2CH.sub.2-3 0 0 524 Cl H H
2-C(--CH.sub.2CH.sub.2--)--CH.sub.2CH.sub.2CH.sub.2-3 0 0 525 Cl H
H 2-CH(CH.sub.2)CH--CH.sub.2CH.sub.2-3 0 0 526 Cl H H
2-CH(OMe)CH.sub.2CH.sub.2CH.sub.2-3 0 0 527 Cl H H
2-CH.dbd.CHCH.dbd.CH-3 0 0 528 Cl H H 2-CH.sub.2CH.sub.2O-3 0 0 529
Cl H H 2-CHMeCH.sub.2O-3 0 0 530 Cl H H 2-CH.sub.2CHMeO-3 0 0 531
Cl H H 2-CH.dbd.CH--O-3 0 0 532 Cl H H 2-CMe.dbd.CH--O-3 0 0 533 Cl
H H 2-CH.dbd.CMe-O-3 0 0 534 Cl H H 2-CH.dbd.CH--S-3 0 0 535 Cl H H
2-N.dbd.CHCH.dbd.CH-3 0 0 (Isomer A) 536 Cl H H
2-N.dbd.CHCH.dbd.CH-3 0 0 (Isomer B) 537 Cl H H 2-N.dbd.CH--O-3 0 0
538 Cl H H 2-N.dbd.CMe--O-3 0 0 539 Cl H H 2-OCH.sub.2CH.sub.2-3 0
0 540 Cl H H 2-OCMe.sub.2CH.sub.2-3 0 0 541 Cl H H 2-OCH.dbd.CH-3 0
0 542 Cl H H 2-OCMe.dbd.CH-3 0 0 543 Cl H H 2-OCF.sub.2O-3 0 0 544
Cl H H 2-OCH.sub.2O-3 0 0 545 Cl H H 2-OCHMeO-3 0 0 546 Cl H H
2-OCMe.sub.2O-3 0 0 547 Cl H H 2-OCH.sub.2CH.sub.2O-3 0 0 548 Cl H
H 2-OCH.dbd.N-3 0 0 549 Cl H H 2-OCMe.dbd.N-3 0 0 550 Cl H H
2,4-F.sub.2 0 0 551 Cl H H 2-Cl, 4-F 0 0 552 Cl H H 2,4-Cl.sub.2 0
0 553 Cl H H 2-Br, 4-F 0 0 554 Cl H H 2,4-Br.sub.2 0 0 555 Cl H H
2-Br, 4-Me 0 0 556 Cl H H 2-Br, 4-tBu 0 0 557 Cl H H 2-Me, 4-F 0 0
558 Cl H H 2-Me, 4-Cl 0 0 559 Cl H H 2,4-Me.sub.2 0 0 560 Cl H H
2-Et, 4-F 0 0 561 Cl H H 2-Et, 4-Cl 0 0 562 Cl H H 2-Et, 4-I 0 0
563 Cl H H 2-Et, 4-Me 0 0 564 Cl H H 2-iPr, 4-F 0 0 565 Cl H H
2-iPr, 4-Cl 0 0 566 Cl H H 2-iPr, 4-Br 0 0 567 Cl H H 2-tBu, 4-Me 0
0 568 Cl H H 2-cPr, 4-F 0 0 569 Cl H H 2-cPr, 4-Cl 0 0 570 Cl H H
2-cPr, 4-Br 0 0 571 Cl H H 2-cPr, 4-Me 0 0 572 Cl H H 2-cPr, 4-Et 0
0 573 Cl H H 2-cPr, 4-CF.sub.3 0 0 574 Cl H H 2-cPr, 4-CN 0 0 575
Cl H H 2-cPr, 4-CO.sub.2Me 0 0 576 Cl H H 2-cPr, 4-NO.sub.2 0 0 577
Cl H H 2-cPr, 4-OMe 0 0 578 Cl H H 2-cBu, 4-F 0 0 579 Cl H H 2-cBu,
4-Cl 0 0 580 Cl H H 2-cBu, 4-Br 0 0 581 Cl H H 2-cBu, 4-Me 0 0 582
Cl H H 2-CF.sub.3, 4-F 0 0 583 Cl H H 2-CF.sub.3, 4-Cl 0 0 584 Cl H
H 2-CF.sub.3, 4-Br 0 0 585 Cl H H 2-CF.sub.3, 4-Me 0 0 586 Cl H H
2-CN, 4-F 0 0 587 Cl H H 2-CN, 4-Cl 0 0 588 Cl H H 2-CN, 4-Br 0 0
589 Cl H H 2-CN, 4-Me 0 0 590 Cl H H 2-CO.sub.2Me, 4-F 0 0 591 Cl H
H 2-CO.sub.2Me, 4-Cl 0 0 592 Cl H H 2-CO.sub.2Me, 4-Br 0 0 593 Cl H
H 2-CO.sub.2Me, 4-Me 0 0 594 Cl H H 2-NO.sub.2, 4-F 0 0 595 Cl H H
2-NO.sub.2, 4-Cl 0 0 596 Cl H H 2-NO.sub.2, 4-Br 0 0 597 Cl H H
2-NO.sub.2, 4-Me 0 0 598 Cl H H 2-OMe, 4-F 0 0 599 Cl H H 2-OMe,
4-Cl 0 0 600 Cl H H 2-OMe, 4-Br 0 0 601 Cl H H 2-OMe, 4-Me 0 0 602
Cl H H 2,4-(OMe).sub.2 0 0 603 Cl H H 2,5-F.sub.2 0 0 604 Cl H H
2-F, 5-Cl 0 0 605 Cl H H 2-F, 5-Br 0 0 606 Cl H H 2-F, 5-I 0 0 607
Cl H H 2-F, 5-Me 0 0 608 Cl H H 2-F, 5-CF.sub.3 0 0 609 Cl H H 2-F,
5-OMe 0 0 610 Cl H H 2-Cl, 5-F 0 0 611 Cl H H 2,5-Cl.sub.2 0 0 612
Cl H H 2-Cl, 5-Br 0 0 613 Cl H H 2-Cl, 5-I 0 0 614 Cl H H 2-Cl,
5-Me 0 0 615 Cl H H 2-Cl, 5-CF.sub.3 0 0 616 Cl H H 2-Cl, 5-OMe 0 0
617 Cl H H 2-Me, 5-F 0 0 618 Cl H H 2-Me, 5-Cl 0 0 619 Cl H H 2-Me,
5-Br 0 0 620 Cl H H 2-Me, 5-I 0 0 621 Cl H H 2,5-Me.sub.2 0 0 622
Cl H H 2-Me, 5-Et 0 0 623 Cl H H 2-Me, 5-iPr 0 0 624 Cl H H 2-Me,
5-CF.sub.3 0 0 625 Cl H H 2-Me, 5-CN 0 0 626 Cl H H 2-Me,
5-CO.sub.2H 0 0 627 Cl H H 2-Me, 5-NH.sub.2 0 0 628 Cl H H 2-Me,
5-NMe.sub.2 0 0 629 Cl H H 2-Me, 5-OMe 0 0 630 Cl H H 2-Et, 5-F 0 0
631 Cl H H 2-Et, 5-Cl 0 0 632 Cl H H 2-Et, 5-Br 0 0 633 Cl H H
2-Et, 5-Me 0 0 634 Cl H H 2-Et, 5-CN 0 0 635 Cl H H 2-Et, 5-OMe 0 0
636 Cl H H 2-iPr, 5-F 0 0 637 Cl H H 2-iPr, 5-Cl 0 0 638 Cl H H
2-iPr, 5-Br 0 0 639 Cl H H 2-iPr, 5-I 0 0 640 Cl H H 2-iPr, 5-Me 0
0 641 Cl H H 2-iPr, 5-Et 0 0 642 Cl H H 2-iPr, 5-iPr 0 0 643 Cl H H
2-iPr, 5-CF.sub.3 0 0 644 Cl H H 2-iPr, 5-CN 0 0 645 Cl H H 2-iPr,
5-OMe 0 0 646 Cl H H 2-tBu, 5-F 0 0 647 Cl H H 2-tBu, 5-Cl 0 0 648
Cl H H 2-tBu, 5-Br 0 0 649 Cl H H 2-tBu, 5-I 0 0 650 Cl H H 2-tBu,
5-Me 0 0 651 Cl H H 2-tBu, 5-Et 0 0 652 Cl H H 2-tBu, 5-iPr 0 0 653
Cl H H 2-tBu, 5-tBu 0 0 654 Cl H H 2-tBu, 5-cPr 0 0 655 Cl H H
2-tBu, 5-CF.sub.3 0 0 656 Cl H H 2-tBu, 5-CN 0 0 657 Cl H H 2-tBu,
5-OMe 0 0 658 Cl H H 2-cPr, 5-F 0 0 659 Cl H H 2-cPr, 5-Cl 0 0 660
Cl H H 2-cPr, 5-Br 0 0 661 Cl H H 2-cPr, 5-I 0 0 662 Cl H H 2-cPr,
5-Me 0 0 663 Cl H H 2-cPr, 5-Et 0 0 664 Cl H H 2-cPr, 5-iPr 0 0 665
Cl H H 2-cPr, 5-tBu 0 0 666 Cl H H 2-cPr, 5-CF.sub.3 0 0 667 Cl H H
2-cPr, 5-CN 0 0 668 Cl H H 2-cPr, 5-OMe 0 0 669 Cl H H 2-CF.sub.3,
5-F 0 0 670 Cl H H 2-CF.sub.3, 5-Cl 0 0 671 Cl H H 2-CF.sub.3, 5-Br
0 0 672 Cl H H 2-CF.sub.3, 5-I 0 0 673 Cl H H 2-CF.sub.3, 5-Me 0 0
674 Cl H H 2-CF.sub.3, 5-CN 0 0 675 Cl H H 2-CF.sub.3, 5-OMe 0 0
676 Cl H H 2-CH.dbd.CH.sub.2, 5-F 0 0 677 Cl H H 2-CH.dbd.CH.sub.2,
5-Cl 0 0 678 Cl H H 2-CHCH.sub.2, 5-Me 0 0 679 Cl H H 2-C.dbd.CHMe,
5-F 0 0 680 Cl H H 2-CH.dbd.CHMe, 5-Cl 0 0 681 Cl H H
2-CH.dbd.CHMe, 5-Me 0 0 682 Cl H H 2-CMe.dbd.CH.sub.2, 5-F 0 0 683
Cl H H 2-CMe.dbd.CH.sub.2, 5-Cl 0 0 684 Cl H H 2-CMe.dbd.CH.sub.2,
5-Me 0 0 685 Cl H H 2-CN, 5-F 0 0 686 Cl H H 2-CN, 5-Cl 0 0 687 Cl
H H 2-CN, 5-Br 0 0 688 Cl H H 2-CN, 5-I 0 0 689 Cl H H 2-CN, 5-Me 0
0 690 Cl H H 2-CN, 5-CN 0 0 691 Cl H H 2-CN, 5-OMe 0 0 692 Cl H H
2-CHO, 5-NMe.sub.2 0 0 693 Cl H H 2-CO.sub.2Me, 5-F 0 0 694 Cl H H
2-CO.sub.2Me, 5-Cl 0 0 695 Cl H H 2-CO.sub.2Me, 5-Br 0 0 696 Cl H H
2-CO.sub.2Me, 5-I 0 0 697 Cl H H 2-CO.sub.2Me, 5-Me 0 0 698 Cl H H
2-CO.sub.2Me, 5-CN 0 0 699 Cl H H 2-CO.sub.2Me, 5-OMe 0 0 700 Cl H
H 2-OMe, 5-F 0 0 701 Cl H H 2-OMe, 5-Cl 0 0 702 Cl H H 2-OMe, 5-Br
0 0 703 Cl H H 2-OMe, 5-I 0 0 704 Cl H H 2-OMe, 5-Me 0 0 705 Cl H H
2-OMe, 5-Et 0 0 706 Cl H H 2-OMe, 5-CF.sub.3 0 0 707 Cl H H 2-OMe,
5-CN 0 0 708 Cl H H 2-OMe, 5-NO.sub.2 0 0 709 Cl H H 2-OMe, 5-OMe 0
0 710 Cl H H 2,6-F.sub.2 0 0 711 Cl H H 2-F, 6-Cl 0 0 712 Cl H H
2-F, 6-Br 0 0 713 Cl H H 2-F, 6-I 0 0 714 Cl H H 2-F, 6-Me 0 0 715
Cl H H 2-F, 6-Et 0 0 716 Cl H H 2-F, 6-Pr 0 0 717 Cl H H 2-F, 6-iPr
0 0 718 Cl H H 2-F, 6-tBu 0 0 719 Cl H H 2-F, 6-cPr 0 0 720 Cl H H
2-F, 6-cBu 0 0 721 Cl H H 2-F, 6-cPen 0 0 722 Cl H H 2-F,
6-CF.sub.3 0 0 723 Cl H H 2-F, 6-CH.sub.2OMe 0 0 724 Cl H H 2-F,
6-CH.sub.2OEt 0 0 725 Cl H H 2-F, 6-CH.sub.2CH.sub.2OMe 0 0 726 Cl
H H 2-F, 6-CH.sub.2SMe 0 0 727 Cl H H 2-F, 6-CH.sub.2SEt 0 0 728 Cl
H H 2-F, 6-CHMeSEt 0 0 729 Cl H H 2-F, 6-CN 0 0 730 Cl H H 2-F,
6-CO.sub.2Me 0 0 731 Cl H H 2-F, 6-NO.sub.2 0 0 732 Cl H H 2-F,
6-OMe 0 0 733 Cl H H 2,6-Cl.sub.2 0 0 734 Cl H H 2-Cl, 6-Br 0 0 735
Cl H H 2-Cl, 6-I 0 0 736 Cl H H 2-Cl, 6-Me 0 0 737 Cl H H 2-Cl,
6-Et 0 0 738 Cl H H 2-Cl, 6-iPr 0 0 739 Cl H H 2-Cl, 6-tBu 0 0 740
Cl H H 2-Cl, 6-cPr 0 0 741 Cl H H 2-Cl, 6-cBu 0 0
742 Cl H H 2-Cl, 6-cPen 0 0 743 Cl H H 2-Cl, 6-CF.sub.3 0 0 744 Cl
H H 2-Cl, 6-CH.dbd.CH.sub.2 0 0 745 Cl H H 2-Cl,
6-CH.sub.2CH.dbd.CH.sub.2 0 0 746 Cl H H 2-Cl,
6-CH.sub.2CMe.dbd.CH.sub.2 0 0 747 Cl H H 2-Cl, 6-CH.sub.2OMe 0 0
748 Cl H H 2-Cl, 6-CH.sub.2OEt 0 0 749 Cl H H 2-Cl,
6-CH.sub.2CH.sub.2OMe 0 0 750 Cl H H 2-Cl, 6-CH.sub.2SMe 0 0 751 Cl
H H 2-Cl, 6-CH.sub.2SEt 0 0 752 Cl H H 2-Cl, 6-CN 0 0 753 Cl H H
2-Cl, 6-CO.sub.2Me 0 0 754 Cl H H 2-Cl, 6-NO.sub.2 0 0 755 Cl H H
2-Cl, 6-OMe 0 0 756 Cl H H 2,6-Br.sub.2 0 0 757 Cl H H 2-Br, 6-I 0
0 758 Cl H H 2-Br, 6-Me 0 0 759 Cl H H 2-Br, 6-Et 0 0 760 Cl H H
2-Br, 6-iPr 0 0 761 Cl H H 2-Br, 6-tBu 0 0 762 Cl H H 2-Br, 6-cPr 0
0 763 Cl H H 2-Br, 6-cBu 0 0 764 Cl H H 2-Br, 6-cPen 0 0 765 Cl H H
2-Br, 6-cHx 0 0 766 Cl H H 2-Br, 6-CF.sub.3 0 0 767 Cl H H 2-Br,
6-CH.dbd.CH.sub.2 0 0 768 Cl H H 2-Br, 6-CH.sub.2CH.dbd.CH.sub.2 0
0 769 Cl H H 2-Br, 6-CH.sub.2CMe.dbd.CH.sub.2 0 0 770 Cl H H 2-Br,
6-CH.sub.2OMe 0 0 771 Cl H H 2-Br, 6-CH.sub.2OEt 0 0 772 Cl H H
2-Br, 6-CH.sub.2CH.sub.2OMe 0 0 773 Cl H H 2-Br, 6-CH.sub.2SMe 0 0
774 Cl H H 2-Br, 6-CH.sub.2SEt 0 0 775 Cl H H 2-Br, 6-CN 0 0 776 Cl
H H 2-Br, 6-CO.sub.2Me 0 0 777 Cl H H 2-Br, 6-NO.sub.2 0 0 778 Cl H
H 2-Br, 6-OMe 0 0 779 Cl H H 2,6-I.sub.2 0 0 780 Cl H H 2-I, 6-Me 0
0 781 Cl H H 2-I, 6-Et 0 0 782 Cl H H 2-I, 6-iPr 0 0 783 Cl H H
2-I, 6-tBu 0 0 784 Cl H H 2-I, 6-cPr 0 0 785 Cl H H 2-I, 6-cBu 0 0
786 Cl H H 2-I, 6-cPen 0 0 787 Cl H H 2-I, 6-cHx 0 0 788 Cl H H
2-I, 6-CF.sub.3 0 0 789 Cl H H 2-I, 6-CH.dbd.CH.sub.2 0 0 790 Cl H
H 2-I, 6-CH.sub.2CH.dbd.CH.sub.2 0 0 791 Cl H H 2-I,
6-CH.sub.2CMe.dbd.CH.sub.2 0 0 792 Cl H H 2-I, 6-CH.sub.2OMe 0 0
793 Cl H H 2-I, 6-CH.sub.2OEt 0 0 794 Cl H H 2-I,
6-CH.sub.2CH.sub.2OMe 0 0 795 Cl H H 2-I, 6-CH.sub.2SMe 0 0 796 Cl
H H 2-I, 6-CH.sub.2SEt 0 0 797 Cl H H 2-I, 6-CN 0 0 798 Cl H H 2-I,
6-CO.sub.2Me 0 0 799 Cl H H 2-I, 6-NO.sub.2 0 0 800 Cl H H 2-I,
6-OMe 0 0 801 Cl H H 2,6-Me.sub.2 0 0 802 Cl H H 2-Me, 6-Et 0 0 803
Cl H H 2-Me, 6-iPr 0 0 804 Cl H H 2-Me, 6-sBu 0 0 805 Cl H H 2-Me,
6-tBu 0 0 806 Cl H H 2-Me, 6-cPr 0 0 807 Cl H H 2-Me, 6-(cPr-1-F) 0
0 808 Cl H H 2-Me, 6-(cPr-1-Cl) 0 0 809 Cl H H 2-Me, 6-(cPr-1-Br) 0
0 810 Cl H H 2-Me, 6-(cPr-1-I) 0 0 811 Cl H H 2-Me, 6-(cPr-1-Me) 0
0 812 Cl H H 2-Me, 6-(cPr-1-Et) 0 0 813 Cl H H 2-Me, 6-(cPr-1-cPr)
0 0 814 Cl H H 2-Me, 6-(cPr-1-CN) 0 0 815 Cl H H 2-Me,
6-(cPr-1-OMe) 0 0 816 Cl H H 2-Me, 6-(cPr-1-OEt) 0 0 817 Cl H H
2-Me, 6-(cPr-2-Me) 0 0 818 Cl H H 2-Me, 6-(cPr-2-Et) 0 0 819 Cl H H
2-Me, 6-(cPr-2-CN) 0 0 820 Cl H H 2-Me, 6-(cPr-2-OMe) 0 0 821 Cl H
H 2-Me, 6-(cPr-2-OEt) 0 0 822 Cl H H 2-Me, 6-(cPr-2-OCF.sub.3) 0 0
823 Cl H H 2-Me, 6-(cPr-1,2-Me.sub.2) 0 0 824 Cl H H 2-Me,
6-{cPr-1,2-(CN).sub.2} 0 0 825 Cl H H -Me, 6-(cPr-2,2-Me.sub.2) 0 0
826 Cl H H 2-Me, 6-(cPr-2,2-F.sub.2) 0 0 827 Cl H H 2-Me,
6-(cPr-2,2-Cl.sub.2) 0 0 828 Cl H H 2-Me, 6-(cPr-2,2-Br.sub.2) 0 0
829 Cl H H 2-Me, 6-{cPr-2,2-(CN).sub.2} 0 0 830 Cl H H 2-Me, 6-cBu
0 0 831 Cl H H 2-Me, 6-cPen 0 0 832 Cl H H 2-Me, 6-cHx 0 0 833 Cl H
H 2-Me, 6-CF.sub.3 0 0 834 Cl H H 2-Me, 6-CH.dbd.CH.sub.2 0 0 835
Cl H H 2-Me, 6-CH.sub.2CH.dbd.CH.sub.2 0 0 836 Cl H H 2-Me,
6-CH.dbd.CH--NO.sub.2 0 0 837 Cl H H 2-Me, 6-CH.sub.2OMe 0 0 838 Cl
H H 2-Me, 6-CH.sub.2OEt 0 0 839 Cl H H 2-Me, 6-CH.sub.2CH.sub.2OMe
0 0 840 Cl H H 2-Me, 6-CH.sub.2SMe 0 0 841 Cl H H 2-Me,
6-CH.sub.2SEt 0 0 842 Cl H H 2-Me, 6-CN 0 0 843 Cl H H 2-Me,
6-CO.sub.2Me 0 0 844 Cl H H 2-Me, 6-NO.sub.2 0 0 845 Cl H H 2-Me,
6-OMe 0 0 846 Cl H H 2,6-Et2 0 0 847 Cl H H 2-Et, 6-iPr 0 0 848 Cl
H H 2-Et, 6-sBu 0 0 849 Cl H H 2-Et, 6-tBu 0 0 850 Cl H H 2-Et,
6-cPr 0 0 851 Cl H H 2-Et, 6-(cPr-1-F) 0 0 852 Cl H H 2-Et,
6-(cPr-1-Cl) 0 0 853 Cl H H 2-Et, 6-(cPr-1-Br) 0 0 854 Cl H H 2-Et,
6-(cPr-1-I) 0 0 855 Cl H H 2-Et, 6-(cPr-1-Me) 0 0 856 Cl H H 2-Et,
6-(cPr-1-Et) 0 0 857 Cl H H 2-Et, 6-(cPr-1-cPr) 0 0 858 Cl H H
2-Et, 6-(cPr-1-CN) 0 0 859 Cl H H 2-Et, 6-(cPr-1-OMe) 0 0 860 Cl H
H 2-Et, 6-(cPr-1-OEt) 0 0 861 Cl H H 2-Et, 6-(cPr-2-Me) 0 0 862 Cl
H H 2-Et, 6-(cPr-2-Et) 0 0 863 Cl H H 2-Et, 6-(cPr-2-CN) 0 0 864 Cl
H H 2-Et, 6-(cPr-2-OMe) 0 0 865 Cl H H 2-Et, 6-(cPr-2-OEt) 0 0 866
Cl H H 2-Et, 6-(cPr-2-OCF.sub.3) 0 0 867 Cl H H 2-Et,
6-(cPr-1,2-Me.sub.2) 0 0 868 Cl H H 2-Et, 6-{cPr-1,2-(CN).sub.2} 0
0 869 Cl H H 2-Et, 6-(cPr-2,2-Me.sub.2) 0 0 870 Cl H H 2-Et,
6-(cPr-2,2-F.sub.2) 0 0 871 Cl H H 2-Et, 6-(cPr-2,2-Cl.sub.2) 0 0
872 Cl H H 2-Et, 6-(cPr-2,2-Br.sub.2) 0 0 873 Cl H H 2-Et,
6-{cPr-2,2-(CN).sub.2} 0 0 874 Cl H H 2-Et, 6-cBu 0 0 875 Cl H H
2-Et, 6-cPen 0 0 876 Cl H H 2-Et, 6-cHx 0 0 877 Cl H H 2-Et,
6-CF.sub.3 0 0 878 Cl H H 2-Et, 6-CH.dbd.CH.sub.2 0 0 879 Cl H H
2-Et, 6-CH.sub.2CH.dbd.CH.sub.2 0 0 880 Cl H H 2-Et,
6-CH.sub.2CMe.dbd.CH.sub.2 0 0 881 Cl H H 2-Et, 6-CH.sub.2OMe 0 0
882 Cl H H 2-Et, 6-CH.sub.2OEt 0 0 883 Cl H H 2-Et,
6-CH.sub.2CH.sub.2OMe 0 0 884 Cl H H 2-Et, 6-CH.sub.2SMe 0 0 885 Cl
H H 2-Et, 6-CH.sub.2SEt 0 0 886 Cl H H 2-Et, 6-CN 0 0 887 Cl H H
2-Et, 6-CO.sub.2Me 0 0 888 Cl H H 2-Et, 6-NO.sub.2 0 0 889 Cl H H
2-Et, 6-OMe 0 0 890 Cl H H 2,6-Pr.sub.2 0 0 891 Cl H H 2-Pr, 6-iPr
0 0 892 Cl H H 2-Pr, 6-tBu 0 0 893 Cl H H 2-Pr, 6-cPr 0 0 894 Cl H
H 2,6-iPr.sub.2 0 0 895 Cl H H 2-iPr, 6-tBu 0 0 896 Cl H H 2-iPr,
6-cPr 0 0 897 Cl H H 2-iPr, 6-cBu 0 0 898 Cl H H 2-iPr, 6-cPen 0 0
899 Cl H H 2-iPr, 6-cHx 0 0 900 Cl H H 2-iPr, 6-CF.sub.3 0 0 901 Cl
H H 2-iPr, 6-CH.dbd.CH.sub.2 0 0 902 Cl H H 2-iPr,
6-CH.sub.2CH.dbd.CH.sub.2 0 0 903 Cl H H 2-iPr,
6-CH.sub.2CMe.dbd.CH.sub.2 0 0 904 Cl H H 2-iPr, 6-CH.sub.2OMe 0 0
905 Cl H H 2-iPr, 6-CH.sub.2OEt 0 0 906 Cl H H 2-iPr,
6-CH.sub.2CH.sub.2OMe 0 0 907 Cl H H 2-iPr, 6-CH.sub.2SMe 0 0 908
Cl H H 2-iPr, 6-CH.sub.2SEt 0 0 909 Cl H H 2-iPr, 6-CN 0 0 910 Cl H
H 2-iPr, 6-CO.sub.2Me 0 0 911 Cl H H 2-iPr, 6-NO.sub.2 0 0 912 Cl H
H 2-iPr, 6-OMe 0 0 913 Cl H H 2,6-tBu.sub.2 0 0 914 Cl H H 2-tBu,
6-cPr 0 0 915 Cl H H 2-tBu, 6-cBu 0 0 916 Cl H H 2-tBu, 6-cPen 0 0
917 Cl H H 2-tBu, 6-cHx 0 0 918 Cl H H 2-tBu, 6-CF.sub.3 0 0 919 Cl
H H 2-tBu, 6-CH.dbd.CH.sub.2 0 0 920 Cl H H 2-tBu,
6-CH.sub.2CH.dbd.CH.sub.2 0 0 921 Cl H H 2-tBu,
6-CH.sub.2CMe.dbd.CH.sub.2 0 0 922 Cl H H 2-tBu, 6-CH.sub.2OMe 0 0
923 Cl H H 2-tBu, 6-CH.sub.2OEt 0 0 924 Cl H H 2-tBu,
6-CH.sub.2CH.sub.2OMe 0 0 925 Cl H H 2-tBu, 6-CH.sub.2SMe 0 0 926
Cl H H 2-tBu, 6-CH.sub.2SEt 0 0 927 Cl H H 2-tBu, 6-CN 0 0 928 Cl H
H 2-tBu, 6-CO.sub.2Me 0 0 929 Cl H H 2-tBu, 6-NO.sub.2 0 0 930 Cl H
H 2-tBu, 6-OMe 0 0 931 Cl H H 2,6-cPr.sub.2 0 0 932 Cl H H 2-cPr,
6-(cPr-1-cPr) 0 0 933 Cl H H 2-cPr, 6-(cPr-1-CN) 0 0 934 Cl H H
2-cPr, 6-(cPr-1-OMe) 0 0 935 Cl H H 2-cPr, 6-(cPr-1-OEt) 0 0 936 Cl
H H 2-cPr, 6-(cPr-2-Me) 0 0 937 Cl H H 2-cPr, 6-(cPr-2-Et) 0 0 938
Cl H H 2-cPr, 6-(cPr-2-CN) 0 0 939 Cl H H 2-cPr, 6-(cPr-2-OMe) 0 0
940 Cl H H 2-cPr, 6-(cPr-2-OEt) 0 0 941 Cl H H 2-cPr,
6-(cPr-2-OCF.sub.3) 0 0 942 Cl H H 2-cPr, 6-(cPr-1,2-Me.sub.2) 0 0
943 Cl H H 2-cPr, 6-{cPr-1,2-(CN).sub.2} 0 0 944 Cl H H 2-cPr,
6-(cPr-2,2-Me.sub.2) 0 0 945 Cl H H 2-cPr, 6-(cPr-2,2-F.sub.2) 0 0
946 Cl H H 2-cPr, 6-(cPr-2,2-Cl.sub.2) 0 0 947 Cl H H 2-cPr,
6-(cPr-2,2-Br.sub.2) 0 0 948 Cl H H 2-cPr, 6-{cPr-2,2-(CN).sub.2} 0
0 949 Cl H H 2-cPr, 6-cBu 0 0 950 Cl H H 2-cPr, 6-cPen 0 0 951 Cl H
H 2-cPr, 6-cHx 0 0 952 Cl H H 2-cPr, 6-CF.sub.3 0 0 953 Cl H H
2-cPr, 6-CH.dbd.CH.sub.2 0 0 954 Cl H H 2-cPr,
6-CH.sub.2CH.dbd.CH.sub.2 0 0 955 Cl H H 2-cPr,
6-CH.sub.2CMe.dbd.CH.sub.2 0 0 956 Cl H H 2-cPr, 6-CH.sub.2OMe 0 0
957 Cl H H 2-cPr, 6-CH.sub.2OEt 0 0 958 Cl H H 2-cPr,
6-CH.sub.2CH.sub.2OMe 0 0 959 Cl H H 2-cPr, 6-CH.sub.2SMe 0 0 960
Cl H H 2-cPr, 6-CH.sub.2SEt 0 0 961 Cl H H 2-cPr, 6-CN 0 0 962 Cl H
H 2-cPr, 6-CO.sub.2Me 0 0 963 Cl H H 2-cPr, 6-NO.sub.2 0 0 964 Cl H
H 2-cPr, 6-OMe 0 0 965 Cl H H 2-cPr, 6-OEt 0 0 966 Cl H H 2-cPr,
6-SMe 0 0 967 Cl H H 2-CF.sub.3, 6-CH.dbd.CH.sub.2 0 0 968 Cl H H
2-CF.sub.3, 6-CH.sub.2CH.dbd.CH.sub.2 0 0 969 Cl H H 2-CF.sub.3,
6-CH.sub.2CMe.dbd.CH.sub.2 0 0 970 Cl H H 2-CF.sub.3, 6-CH.sub.2OMe
0 0 971 Cl H H 2-CF.sub.3, 6-CH.sub.2OEt 0 0 972 Cl H H 2-CF.sub.3,
6-CH.sub.2CH.sub.2OMe 0 0 973 Cl H H 2-CF.sub.3, 6-CH.sub.2SMe 0 0
974 Cl H H 2-CF.sub.3, 6-CH.sub.2SEt 0 0 975 Cl H H 2-CF.sub.3,
6-CN 0 0 976 Cl H H 2-CF.sub.3, 6-CO.sub.2Me 0 0 977 Cl H H
2-CF.sub.3, 6-NO.sub.2 0 0 978 Cl H H 2-CF.sub.3, 6-OMe 0 0 979 Cl
H H 2,6-(CH.dbd.CHMe).sub.2 0 0 980 Cl H H 2-CH.dbd.CHMe, 6-CN 0 0
981 Cl H H 2-CH.dbd.CHMe, 6-OMe 0 0 982 Cl H H
2,6-(CH.sub.2CH.dbd.CH.sub.2).sub.2 0 0 983 Cl H H
2-CH.sub.2CH.dbd.CH.sub.2, 6-CN 0 0 984 Cl H H
2-CH.sub.2CH.dbd.CH.sub.2, 6-OMe 0 0 985 Cl H H 2,6-(CN).sub.2 0 0
986 Cl H H 2-CN, 6-OMe 0 0 987 Cl H H 2,6-(OMe).sub.2 0 0 988 Cl H
H 3,5-F.sub.2 0 0 989 Cl H H 3-F, 5-Cl 0 0 990 Cl H H 3-F, 5-Br 0 0
991 Cl H H 3-F, 5-I 0 0 992 Cl H H 3,5-Cl.sub.2 0 0
993 Cl H H 3-Cl, 5-Br 0 0 994 Cl H H 3-Cl, 5-I 0 0 995 Cl H H
3,5-Br.sub.2 0 0 996 Cl H H 3-Br, 5-I 0 0 997 Cl H H 3,5-I.sub.2 0
0 998 Cl H H 3,5-Me.sub.2 0 0 999 Cl H H 3-Me, 5-Et 0 0 1000 Cl H H
3-Me, 5-iPr 0 0 1001 Cl H H 3-Me, 5-cPr 0 0 1002 Cl H H 3-Me, 5-cBu
0 0 1003 Cl H H 3-Me, 5-CF.sub.3 0 0 1004 Cl H H 3-Me, 5-CN 0 0
1005 Cl H H 3-Me, 5-NO.sub.2 0 0 1006 Cl H H 3-Me, 5-OMe 0 0 1007
Cl H H 3,5-iPr.sub.2 0 0 1008 Cl H H 3-iPr, 5-CF.sub.3 0 0 1009 Cl
H H 3,5-(CF.sub.3).sub.2 0 0 1010 Cl H H 2-F, 3,5-Me.sub.2 0 0 1011
Cl H H 2-Cl, 3,5-Me.sub.2 0 0 1012 Cl H H 2,3,5-Cl.sub.3 0 0 1013
Cl H H 2-Br, 3,5-Me.sub.2 0 0 1014 Cl H H 2-Br, 3,5-Cl.sub.2 0 0
1015 Cl H H 2-I, 3,5-Me.sub.2 0 0 1016 Cl H H 2,3,5-Me.sub.3 0 0
1017 Cl H H 2-Me, 3,5-Cl.sub.2 0 0 1018 Cl H H 2-Et, 3,5-Me.sub.2 0
0 1019 Cl H H 2-Et, 3,5-Cl.sub.2 0 0 1020 Cl H H 2-Pr, 3,5-Me.sub.2
0 0 1021 Cl H H 2-iPr, 3,5-Me.sub.2 0 0 1022 Cl H H 2-iPr,
3,5-Cl.sub.2 0 0 1023 Cl H H 2-cPr, 3,5-Me.sub.2 0 0 1024 Cl H H
2-cBu, 3,5-Me.sub.2 0 0 1025 Cl H H 2-CN, 3,5-Me.sub.2 0 0 1026 Cl
H H 2-OMe, 3,5-Me.sub.2 0 0 1027 Cl H H 2-SMe, 3,5-Me.sub.2 0 0
1028 Cl H H 2-F, 3,6-Me.sub.2 0 0 1029 Cl H H 2-F, 3-Me, 6-cPr 0 0
1030 Cl H H 2-F, 3-Me, 6-OMe 0 0 1031 Cl H H 2-Cl, 3,6-Me.sub.2 0 0
1032 Cl H H 2-Cl, 3-Me, 6-cPr 0 0 1033 Cl H H 2-Cl, 3-Me, 6-OMe 0 0
1034 Cl H H 2,3,6-Cl.sub.3 0 0 1035 Cl H H 2,3-Cl.sub.2, 6-cPr 0 0
1036 Cl H H 2-Br, 3,6-Cl.sub.2 0 0 1037 Cl H H 2,6-Br.sub.2, 3-Cl 0
0 1038 Cl H H 2-Br, 3-Cl, 6-cPr 0 0 1039 Cl H H 2,6-Br.sub.2, 3-Me
0 0 1040 Cl H H 2-Br, 3,6-Me.sub.2 0 0 1041 Cl H H 2-Br, 3-Me,
6-cPr 0 0 1042 Cl H H 2-Br, 3-Me, 6-OMe 0 0 1043 Cl H H 2,2,3-CN 0
0 1044 Cl H H 2-Br, 3-CN, 6-cPr 0 0 1045 Cl H H 2,6-Br.sub.2, 3-OMe
0 0 1046 Cl H H 2-Br, 3-OMe, 6-cPr 0 0 1047 Cl H H 2-I,
3,6-Me.sub.2 0 0 1048 Cl H H 2-Me, 3,6-F.sub.2 0 0 1049 Cl H H
2-Me, 3-F, 6-Cl 0 0 1050 Cl H H 2-Me, 3-F, 6-Br 0 0 1051 Cl H H
2-Me, 3-F, 6-I 0 0 1052 Cl H H 2-Me, 3-F, 6-cPr 0 0 1053 Cl H H
2-Me, 3-Cl, 6-Br 0 0 1054 Cl H H 2-Me, 3-Cl, 6-I 0 0 1055 Cl H H
2-Me, 3-Cl, 6-cPr 0 0 1056 Cl H H 2,3-Me.sub.2, 6-F 0 0 1057 Cl H H
2,3-Me.sub.2, 6-Cl 0 0 1058 Cl H H 2,3-Me.sub.2, 6-Br 0 0 1059 Cl H
H 2,3-Me.sub.2, 6-I 0 0 1060 Cl H H 2,3,6-Me.sub.3 0 0 1061 Cl H H
2,3-Me.sub.2, 6-cPr 0 0 1062 Cl H H 2,3-Me.sub.2, 6-CN 0 0 1063 Cl
H H 2,3-Me.sub.2, 6-CH.dbd.NOMe 0 0 1064 Cl H H 2,3-Me.sub.2, 6-OMe
0 0 1065 Cl H H 2-Me, 3-OMe, 6-Cl 0 0 1066 Cl H H 2-Me, 3-OMe, 6-Br
0 0 1067 Cl H H 2-Me, 3-OMe, 6-I 0 0 1068 Cl H H 2,6-Me.sub.2,
3-OMe 0 0 1069 Cl H H 2-Me, 3-OMe, 6-cPr 0 0 1070 Cl H H 2-cPr,
3-Me, 6-F 0 0 1071 Cl H H 2-cPr, 3-Me, 6-Cl 0 0 1072 Cl H H 2-cPr,
3-Me, 6-Br 0 0 1073 Cl H H 2-cPr, 3,6-Me.sub.2 0 0 1074 Cl H H
2-cPr, 3-Me, 6-Et 0 0 1075 Cl H H 2,6-cPr.sub.2, 3-Me 0 0 1076 Cl H
H 2-cPr, 3-Me, 6-CN 0 0 1077 Cl H H 2-cPr, 3-Me, 6-OMe 0 0 1078 Cl
H H 2-cBu, 3,6-Me.sub.2 0 0 1079 Cl H H 2-CH.sub.2CH.dbd.CH.sub.2,
3,6-Me.sub.2 0 0 1080 Cl H H 2-CH.sub.2CH.dbd.CH.sub.2, 3-OMe, 6-Et
0 0 1081 Cl H H 2-CN, 3,6-Me.sub.2 0 0 1082 Cl H H 2-OMe,
3,6-Me.sub.2 0 0 1083 Cl H H 2-CH.sub.2SMe, 3,6-Me.sub.2 0 0 1084
Cl H H 6-F, 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1085 Cl H H 6-Cl,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1086 Cl H H 6-Br,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1087 Cl H H 6-I,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1088 Cl H H 6-Me,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1089 Cl H H 6-Et,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1090 Cl H H 6-iPr,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1091 Cl H H 6-cPr,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1092 Cl H H 6-CN,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1093 Cl H H 6-OMe,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1094 Cl H H 6-Cl,
2-OCH.sub.2CH.sub.2-3 0 0 1095 Cl H H 6-Br, 2-OCH.sub.2CH.sub.2-3 0
0 1096 Cl H H 6-Me, 2-OCH.sub.2CH.sub.2-3 0 0 1097 Cl H H 6-Et,
2-OCH.sub.2CH.sub.2-3 0 0 1098 Cl H H 6-cPr, 2-OCH.sub.2CH.sub.2-3
0 0 1099 Cl H H 6-Br, 2-OCH.dbd.CH-3 0 0 1100 Cl H H 6-Me,
2-OCH.dbd.CH-3 0 0 1101 Cl H H 6-Et, 2-OCH.dbd.CH-3 0 0 1102 Cl H H
6-cPr, 2-OCH.dbd.CH-3 0 0 1103 Cl H H 6-Cl, 2-CH.sub.2CH.sub.2O-3 0
0 1104 Cl H H 6-Br, 2-CH.sub.2CH.sub.2O-3 0 0 1105 Cl H H 6-Me,
2-CH.sub.2CH.sub.2O-3 0 0 1106 Cl H H 6-Et, 2-CH.sub.2CH.sub.2O-3 0
0 1107 Cl H H 6-cPr, 2-CH.sub.2CH.sub.2O-3 0 0 1108 Cl H H 6-Br,
2-CH.dbd.CHO-3 0 0 1109 Cl H H 6-Me, 2-CH.dbd.CHO-3 0 0 1110 Cl H H
6-Et, 2-CH.dbd.CHO-3 0 0 1111 Cl H H 6-cPr, 2-CH.dbd.CHO-3 0 0 1112
Cl H H 2,4,6-F.sub.3 0 0 1113 Cl H H 2,4-F.sub.2, 6-Me 0 0 1114 Cl
H H 2,4-F.sub.2, 6-cPr 0 0 1115 Cl H H 2-F, 4,6-cPr.sub.2 0 0 1116
Cl H H 2,4,6-Cl.sub.3 0 0 1117 Cl H H 2,4,6-Br.sub.3 0 0 1118 Cl H
H 2,4-Br.sub.2, 3,6-Me.sub.2 0 0 1119 Cl H H 2-Br, 4,6-Me.sub.2 0 0
1120 Cl H H 2,4-I.sub.2, 6-Et 0 0 1121 Cl H H 2-Me, 4-F, 6-cPr 0 0
1122 Cl H H 2,4,6-Me.sub.3 0 0 1123 Cl H H 2,2,6-cPr 0 0 1124 Cl H
H 2-Br, 3,5,6-Me.sub.3 0 0 1125 Cl H H 2,3,5,6-Me.sub.4 0 0 1126 Cl
H H 2,3,3,6-cPr 0 0 1127 Cl H H 2,3,5-Me.sub.3, 6-CN 0 0 1128 Cl H
H 2,3,3,6-OMe 0 0 1129 Cl H H 5,6-Me.sub.2,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1130 Cl H H 5-Me, 6-cPr,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1131 Cl H H 5-Me, 6-CN,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1132 Cl H H 5-Me, 6-OMe,
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1133 Cl H H
2-CH.sub.2CH.sub.2CH.sub.2-3,5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1134
Cl H COMe 2-F 0 0 1135 Cl H COMe 2-Cl 0 0 1136 Cl H COMe 2-Br 0 0
1137 Cl H COMe 2-I 0 0 1138 Cl H COMe 2-Me 0 0 1139 Cl H COMe 2-iPr
0 0 1140 Cl H COMe 2-cPr 0 0 1141 Cl H COMe 2-cBu 0 0 1142 Cl H
COMe 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1143 Cl H COMe 2-cPr, 5-Me 0
0 1144 Cl H COMe 2-OMe, 5-Me 0 0 1145 Cl H COMe 2-F, 6-iPr 0 0 1146
Cl H COMe 2-Cl, 6-cPr 0 0 1147 Cl H COMe 2-Br, 6-Me 0 0 1148 Cl H
COMe 2-I, 6-Me 0 0 1149 Cl H COMe 2,6-Me.sub.2 0 0 1150 Cl H COMe
2-Me, 6-Et 0 0 1151 Cl H COMe 2-Me, 6-cPr 0 0 1152 Cl H COMe
2,6-cPr.sub.2 0 0 1153 Cl H COMe 2-cPr, 3,5-Me.sub.2 0 0 1154 Cl H
COMe 2-cPr, 5,6-Me.sub.2 0 0 1155 Cl H COEt 2-Me 0 0 1156 Cl H COEt
2-iPr 0 0 1157 Cl H COEt 2-cPr 0 0 1158 Cl H COEt
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1159 Cl H COEt 2,6-Me.sub.2 0 0
1160 Cl H COEt 2-Me, 6-cPr 0 0 1161 Cl H COPr 2-Me 0 0 1162 Cl H
COPr 2-iPr 0 0 1163 Cl H COPr 2-cPr 0 0 1164 Cl H COPr
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1165 Cl H COPr 2,6-Me.sub.2 0 0
1166 Cl H COPr 2-Me, 6-cPr 0 0 1167 Cl H COiPr 2-Me 0 0 1168 Cl H
COiPr 2-iPr 0 0 1169 Cl H COiPr 2-cPr 0 0 1170 Cl H COiPr
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1171 Cl H COiPr 2,6-Me.sub.2 0 0
1172 Cl H COiPr 2-Me, 6-cPr 0 0 1173 Cl H COBu 2-Me 0 0 1174 Cl H
COBu 2-iPr 0 0 1175 Cl H COBu 2-cPr 0 0 1176 Cl H COBu
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1177 Cl H COBu 2,6-Me.sub.2 0 0
1178 Cl H COBu 2-Me, 6-cPr 0 0 1179 Cl H COiBu 2-Me 0 0 1180 Cl H
COiBu 2-iPr 0 0 1181 Cl H COiBu 2-cPr 0 0 1182 Cl H COiBu
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1183 Cl H COiBu 2,6-Me.sub.2 0 0
1184 Cl H COiBu 2-Me, 6-cPr 0 0 1185 Cl H COsBu 2-Me 0 0 1186 Cl H
COsBu 2-iPr 0 0 1187 Cl H COsBu 2-cPr 0 0 1188 Cl H COsBu
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1189 Cl H COsBu 2,6-Me.sub.2 0 0
1190 Cl H COsBu 2-Me, 6-cPr 0 0 1191 Cl H COtBu 2-Cl 0 0 1192 Cl H
COtBu 2-Br 0 0 1193 Cl H COtBu 2-I 0 0 1194 Cl H COtBu 2-Me 0 0
1195 Cl H COtBu 2-iPr 0 0 1196 Cl H COtBu 2-cPr 0 0 1197 Cl H COtBu
2-cBu 0 0 1198 Cl H COtBu 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1199 Cl
H COtBu 2-cPr, 5-Me 0 0 1200 Cl H COtBu 2-OMe, 5-Me 0 0 1201 Cl H
COtBu 2-F, 6-iPr 0 0 1202 Cl H COtBu 2-Cl, 6-cPr 0 0 1203 Cl H
COtBu 2-Br, 6-Me 0 0 1204 Cl H COtBu 2-I, 6-Me 0 0 1205 Cl H COtBu
2,6-Me.sub.2 0 0 1206 Cl H COtBu 2-Me, 6-Et 0 0 1207 Cl H COtBu
2-Me, 6-cPr 0 0 1208 Cl H COtBu 2,6-cPr.sub.2 0 0 1209 Cl H COtBu
2-cPr, 3,5-Me.sub.2 0 0 1210 Cl H COtBu 2-cPr, 5,6-Me.sub.2 0 0
1211 Cl H COtPen 2-Me 0 0 1212 Cl H COtPen 2-iPr 0 0 1213 Cl H
COtPen 2-cPr 0 0 1214 Cl H COtPen 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
1215 Cl H COtPen 2,6-Me.sub.2 0 0 1216 Cl H COtPen 2-Me, 6-cPr 0 0
1217 Cl H COHx 2-Me 0 0 1218 Cl H COHx 2-iPr 0 0 1219 Cl H COHx
2-cPr 0 0 1220 Cl H COHx 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1221 Cl H
COHx 2,6-Me.sub.2 0 0 1222 Cl H COHx 2-Me, 6-cPr 0 0 1223 Cl H
COC.sub.7H.sub.15 2-Me 0 0 1224 Cl H COC.sub.7H.sub.15 2-iPr 0 0
1225 Cl H COC.sub.7H.sub.15 2-cPr 0 0 1226 Cl H COC.sub.7H.sub.15
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1227 Cl H COC.sub.7H.sub.15
2,6-Me.sub.2 0 0 1228 Cl H COC.sub.7H.sub.15 2-Me, 6-cPr 0 0 1229
Cl H COC.sub.8H.sub.17 2-Me 0 0 1230 Cl H COC.sub.8H.sub.17 2-iPr 0
0 1231 Cl H COC.sub.8H.sub.17 2-cPr 0 0 1232 Cl H COC.sub.8H.sub.17
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1233 Cl H COC.sub.8H.sub.17
2,6-Me.sub.2 0 0 1234 Cl H COC.sub.8H.sub.17 2-Me, 6-cPr 0 0 1235
Cl H COC.sub.9H.sub.19 2-Cl 0 0 1236 Cl H COC.sub.9H.sub.19 2-Br 0
0 1237 Cl H COC.sub.9H.sub.19 2-I 0 0 1238 Cl H COC.sub.9H.sub.19
2-Me 0 0 1239 Cl H COC.sub.9H.sub.19 2-iPr 0 0 1240 Cl H
COC.sub.9H.sub.19 2-cPr 0 0 1241 Cl H COC.sub.9H.sub.19 2-cBu 0 0
1242 Cl H COC.sub.9H.sub.19 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1243
Cl H COC.sub.9H.sub.19 2-cPr, 5-Me 0 0
1244 Cl H COC.sub.9H.sub.19 2-OMe, 5-Me 0 0 1245 Cl H
COC.sub.9H.sub.19 2-F, 6-iPr 0 0 1246 Cl H COC.sub.9H.sub.19 2-Cl,
6-cPr 0 0 1247 Cl H COC.sub.9H.sub.19 2-Br, 6-Me 0 0 1248 Cl H
COC.sub.9H.sub.19 2-I, 6-Me 0 0 1249 Cl H COC.sub.9H.sub.19
2,6-Me.sub.2 0 0 1250 Cl H COC.sub.9H.sub.19 2-Me, 6-Et 0 0 1251 Cl
H COC.sub.9H.sub.19 2-Me, 6-cPr 0 0 1252 Cl H COC.sub.9H.sub.19
2,6-cPr.sub.2 0 0 1253 Cl H COC.sub.9H.sub.19 2-cPr, 3,5-Me.sub.2 0
0 1254 Cl H COC.sub.9H.sub.19 2-cPr, 5,6-Me.sub.2 0 0 1255 Cl H
COC.sub.14H.sub.29 2-Me 0 0 1256 Cl H COC.sub.14H.sub.29 2-iPr 0 0
1257 Cl H COC.sub.14H.sub.29 2-cPr 0 0 1258 Cl H COC.sub.14H.sub.29
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1259 Cl H COC.sub.14H.sub.29
2,6-Me.sub.2 0 0 1260 Cl H COC.sub.14H.sub.29 2-Me, 6-cPr 0 0 1261
Cl H COcPr 2-Cl 0 0 1262 Cl H COcPr 2-Br 0 0 1263 Cl H COcPr 2-I 0
0 1264 Cl H COcPr 2-Me 0 0 1265 Cl H COcPr 2-iPr 0 0 1266 Cl H
COcPr 2-cPr 0 0 1267 Cl H COcPr 2-cBu 0 0 1268 Cl H COcPr
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1269 Cl H COcPr 2-cPr, 5-Me 0 0
1270 Cl H COcPr 2-OMe, 5-Me 0 0 1271 Cl H COcPr 2-F, 6-iPr 0 0 1272
Cl H COcPr 2-Cl, 6-cPr 0 0 1273 Cl H COcPr 2-Br, 6-Me 0 0 1274 Cl H
COcPr 2-I, 6-Me 0 0 1275 Cl H COcPr 2,6-Me.sub.2 0 0 1276 Cl H
COcPr 2-Me, 6-Et 0 0 1277 Cl H COcPr 2-Me, 6-cPr 0 0 1278 Cl H
COcPr 2,6-cPr.sub.2 0 0 1279 Cl H COcPr 2-cPr, 3,5-Me.sub.2 0 0
1280 Cl H COcPr 2-cPr, 5,6-Me.sub.2 0 0 1281 Cl H COcBu 2-Me 0 0
1282 Cl H COcBu 2-iPr 0 0 1283 Cl H COcBu 2-cPr 0 0 1284 Cl H COcBu
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1285 Cl H COcBu 2,6-Me.sub.2 0 0
1286 Cl H COcBu 2-Me, 6-cPr 0 0 1287 Cl H COcPen 2-Me 0 0 1288 Cl H
COcPen 2-iPr 0 0 1289 Cl H COcPen 2-cPr 0 0 1290 Cl H COcPen
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1291 Cl H COePen 2,6-Me.sub.2 0 0
1292 Cl H COcPen 2-Me, 6-cPr 0 0 1293 Cl H COcHx 2-Me 0 0 1294 Cl H
COcHx 2-iPr 0 0 1295 Cl H COcHx 2-cPr 0 0 1296 Cl H COcHx
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1297 Cl H COcHx 2,6-Me.sub.2 0 0
1298 Cl H COcHx 2-Me, 6-cPr 0 0 1299 Cl H COCF.sub.3 2-Me 0 0 1300
Cl H COCF.sub.3 2-iPr 0 0 1301 Cl H COCF.sub.3 2-cPr 0 0 1302 Cl H
COCF.sub.3 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1303 Cl H COCF.sub.3
2,6-Me.sub.2 0 0 1304 Cl H COCF.sub.3 2-Me, 6-cPr 0 0 1305 Cl H
COCH.sub.2Cl 2-Me 0 0 1306 Cl H COCH.sub.2Cl 2-iPr 0 0 1307 Cl H
COCH.sub.2Cl 2-cPr 0 0 1308 Cl H COCH.sub.2Cl
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1309 Cl H COCH.sub.2Cl
2,6-Me.sub.2 0 0 1310 Cl H COCH.sub.2Cl 2-Me, 6-cPr 0 0 1311 Cl H
COCCl.sub.3 2-Me 0 0 1312 Cl H COCCl.sub.3 2-iPr 0 0 1313 Cl H
COCCl.sub.3 2-cPr 0 0 1314 Cl H COCCl.sub.3
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1315 Cl H COCCl.sub.3 2,6-Me.sub.2
0 0 1316 Cl H COCCl.sub.3 2-Me, 6-cPr 0 0 1317 Cl H COCH.sub.2Br
2-Me 0 0 1318 Cl H COCH.sub.2Br 2-iPr 0 0 1319 Cl H COCH.sub.2Br
2-cPr 0 0 1320 Cl H COCH.sub.2Br 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
1321 Cl H COCH.sub.2Br 2,6-Me.sub.2 0 0 1322 Cl H COCH.sub.2Br
2-Me, 6-cPr 0 0 1323 Cl H COCH.sub.2CF.sub.3 2-Me 0 0 1324 Cl H
COCH.sub.2CF.sub.3 2-iPr 0 0 1325 Cl H COCH.sub.2CF.sub.3 2-cPr 0 0
1326 Cl H COCH.sub.2CF.sub.3 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1327
Cl H COCH.sub.2CF.sub.3 2,6-Me.sub.2 0 0 1328 Cl H
COCH.sub.2CF.sub.3 2-Me, 6-cPr 0 0 1329 Cl H COCHBrEt 2-Me 0 0 1330
Cl H COCHBrEt 2-iPr 0 0 1331 Cl H COCHBrEt 2-cPr 0 0 1332 Cl H
COCHBrEt 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1333 Cl H COCHBrEt
2,6-Me.sub.2 0 0 1334 Cl H COCHBrEt 2-Me, 6-cPr 0 0 1335 Cl H
COCH.sub.2CH.sub.2CH.sub.2Cl 2-Me 0 0 1336 Cl H
COCH.sub.2CH.sub.2CH.sub.2Cl 2-iPr 0 0 1337 Cl H
COCH.sub.2CH.sub.2CH.sub.2Cl 2-cPr 0 0 1338 Cl H
COCH.sub.2CH.sub.2CH.sub.2Cl 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1339
Cl H COCH.sub.2CH.sub.2CH.sub.2Cl 2,6-Me.sub.2 0 0 1340 Cl H
COCH.sub.2CH.sub.2CH.sub.2Cl 2-Me, 6-cPr 0 0 1341 Cl H
COCH.dbd.CH.sub.2 2-Me 0 0 1342 Cl H COCH.dbd.CH.sub.2 2-iPr 0 0
1343 Cl H COCH.dbd.CH.sub.2 2-cPr 0 0 1344 Cl H COCH.dbd.CH.sub.2
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1345 Cl H COCH.dbd.CH.sub.2
2,6-Me.sub.2 0 0 1346 Cl H COCH.dbd.CH.sub.2 2-Me, 6-cPr 0 0 1347
Cl H COCH.dbd.CHMe 2-Me 0 0 1348 Cl H COCH.dbd.CHMe 2-iPr 0 0 1349
Cl H COCH.dbd.CHMe 2-cPr 0 0 1350 Cl H COCH.dbd.CHMe
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1351 Cl H COCH.dbd.CHMe
2,6-Me.sub.2 0 0 1352 Cl H COCH.dbd.CHMe 2-Me, 6-cPr 0 0 1353 Cl H
COCH.dbd.CMe.sub.2 2-Me 0 0 1354 Cl H COCH.dbd.CMe.sub.2 2-iPr 0 0
1355 Cl H COCH.dbd.CMe.sub.2 2-cPr 0 0 1356 Cl H COCH.dbd.CMe.sub.2
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1357 Cl H COCH.dbd.CMe.sub.2
2,6-Me.sub.2 0 0 1358 Cl H COCH.dbd.CMe.sub.2 2-Me, 6-cPr 0 0 1359
Cl H COCH.dbd.CHPh 2-Me 0 0 1360 Cl H COCH.dbd.CHPh 2-iPr 0 0 1361
Cl H COCH.dbd.CHPh 2-cPr 0 0 1362 Cl H COCH.dbd.CHPh
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1363 Cl H COCH.dbd.CHPh
2,6-Me.sub.2 0 0 1364 Cl H COCH.dbd.CHPh 2-Me, 6-cPr 0 0 1365 Cl H
COC CH 2-Me 0 0 1366 Cl H COC CH 2-iPr 0 0 1367 Cl H COC CH 2-cPr 0
0 1368 Cl H COC CH 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1369 Cl H COC
CH 2,6-Me.sub.2 0 0 1370 Cl H COC CH 2-Me, 6-cPr 0 0 1371 Cl H
COCH.sub.2Ph 2-Me 0 0 1372 Cl H COCH.sub.2Ph 2-iPr 0 0 1373 Cl H
COCH.sub.2Ph 2-cPr 0 0 1374 Cl H COCH.sub.2Ph
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1375 Cl H COCH.sub.2Ph
2,6-Me.sub.2 0 0 1376 Cl H COCH.sub.2Ph 2-Me, 6-cPr 0 0 1377 Cl H
COCH.sub.2CH.sub.2CO.sub.2Me 2-Me 0 0 1378 Cl H
COCH.sub.2CH.sub.2CO.sub.2Me 2-iPr 0 0 1379 Cl H
COCH.sub.2CH.sub.2CO.sub.2Me 2-cPr 0 0 1380 Cl H
COCH.sub.2CH.sub.2CO.sub.2Me 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1381
Cl H COCH.sub.2CH.sub.2CO.sub.2Me 2,6-Me.sub.2 0 0 1382 Cl H
COCH.sub.2CH.sub.2CO.sub.2Me 2-Me, 6-cPr 0 0 1383 Cl H COPh 2-F 0 0
1384 Cl H COPh 2-Cl 0 0 1385 Cl H COPh 2-Br 0 0 1386 Cl H COPh 2-I
0 0 1387 Cl H COPh 2-Me 0 0 1388 Cl H COPh 2-Et 0 0 1389 Cl H COPh
2-iPr 0 0 1390 Cl H COPh 2-tBu 0 0 1391 Cl H COPh 2-cPr 0 0 1392 Cl
H COPh 2-(cPr-1-Me) 0 0 1393 Cl H COPh 2-(cPr-2-Me) 0 0 1394 Cl H
COPh 2-(cPr-2,2-Cl.sub.2) 0 0 1395 Cl H COPh 2-cBu 0 0 1396 Cl H
COPh 4-SiMe.sub.3 0 0 1397 Cl H COPh 2-CH.sub.2CH.sub.2CH.sub.2-3 0
0 1398 Cl H COPh 2-CH.dbd.CHO-3 0 0 1399 Cl H COPh
2-CH.sub.2CH.sub.2O-3 0 0 1400 Cl H COPh 2-OCH.dbd.CH-3 0 0 1401 Cl
H COPh 2-OCH.sub.2CH.sub.2-3 0 0 1402 Cl H COPh 2-cPr, 5-F 0 0 1403
Cl H COPh 2-cPr, 5-Cl 0 0 1404 Cl H COPh 2-cPr, 5-Me 0 0 1405 Cl H
COPh 2-OMe, 5-Me 0 0 1406 Cl H COPh 2-F, 6-iPr 0 0 1407 Cl H COPh
2-F, 6-cPr 0 0 1408 Cl H COPh 2-Cl, 6-Me 0 0 1409 Cl H COPh 2-Cl,
6-cPr 0 0 1410 Cl H COPh 2-Br, 6-Me 0 0 1411 Cl H COPh 2-Br, 6-Et 0
0 1412 Cl H COPh 2-Br, 6-cPr 0 0 1413 Cl H COPh 2-I, 6-Me 0 0 1414
Cl H COPh 2-I, 6-Et 0 0 1415 Cl H COPh 2,6-Me.sub.2 0 0 1416 Cl H
COPh 2-Me, 6-Et 0 0 1417 Cl H COPh 2-Me, 6-cPr 0 0 1418 Cl H COPh
2-Et, 6-cPr 0 0 1419 Cl H COPh 2-iPr, 6-cPr 0 0 1420 Cl H COPh
2-tBu, 6-cPr 0 0 1421 Cl H COPh 2,6-cPr.sub.2 0 0 1422 Cl H COPh
2-cPr, 6-OMe 0 0 1423 Cl H COPh 2-Br, 3,6-Me.sub.2 0 0 1424 Cl H
COPh 2-cPr, 3,5-Me.sub.2 0 0 1425 Cl H COPh 2-cPr,4, 6-Me.sub.2 0 0
1426 Cl H COPh 2-Br, 5,6-Me.sub.2 0 0 1427 Cl H COPh 2-cPr,
5,6-Me.sub.2 0 0 1428 Cl H COPh 2-Br, 5-CH.dbd.CH--O-6 0 0 1429 Cl
H COPh 2-Me, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1430 Cl H COPh 2-Me,
5-CH.sub.2CH.sub.2O-6 0 0 1431 Cl H COPh 2-Me, 5-CH.dbd.CH--O-6 0 0
1432 Cl H COPh 2-Et, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1433 Cl H
COPh 2-cPr, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1434 Cl H COPh 2-cPr,
5-CH.dbd.CH--O-6 0 0 1435 Cl H COPh 2-Br, 3,5,6-Me.sub.3 0 0 1436
Cl H CO(Ph-2-Cl) 2-Me 0 0 1437 Cl H CO(Ph-2-Cl) 2-iPr 0 0 1438 Cl H
CO(Ph-2-Cl) 2-cPr 0 0 1439 Cl H CO(Ph-2-Cl)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1440 Cl H CO(Ph-2-Cl) 2,6-Me.sub.2
0 0 1441 Cl H CO(Ph-2-Cl) 2-Me, 6-cPr 0 0 1442 Cl H CO(Ph-2-Me) 2-F
0 0 1443 Cl H CO(Ph-2-Me) 2-Cl 0 0 1444 Cl H CO(Ph-2-Me) 2-Br 0 0
1445 Cl H CO(Ph-2-Me) 2-I 0 0 1446 Cl H CO(Ph-2-Me) 2-Me 0 0 1447
Cl H CO(Ph-2-Me) 2-Et 0 0 1448 Cl H CO(Ph-2-Me) 2-iPr 0 0 1449 Cl H
CO(Ph-2-Me) 2-tBu 0 0 1450 Cl H CO(Ph-2-Me) 2-sBu 0 0 1451 Cl H
CO(Ph-2-Me) 2-(cPr-1-Me) 0 0 1452 Cl H CO(Ph-2-Me) 2-cPr 0 0 1453
Cl H CO(Ph-2-Me) 2-(cPr-2,2-Cl.sub.2) 0 0 1454 Cl H CO(Ph-2-Me)
2-cBu 0 0 1455 Cl H CO(Ph-2-Me) 2-cHx 0 0 1456 Cl H CO(Ph-2-Me)
2-Ph 0 0 1457 Cl H CO(Ph-2-Me) 3-tBu 0 0 1458 Cl H CO(Ph-2-Me)
3-OMe 0 0 1459 Cl H CO(Ph-2-Me) 2-iPr, 5-Me 0 0 1460 Cl H
CO(Ph-2-Me) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1461 Cl H CO(Ph-2-Me)
2-CH.dbd.CH.dbd.CH.dbd.CH-3 0 0 1462 Cl H CO(Ph-2-Me)
2-CH.dbd.CHO-3 0 0 1463 Cl H CO(Ph-2-Me) 2-CH.sub.2CH.sub.2O-3 0 0
1464 Cl H CO(Ph-2-Me) 2-OCH.dbd.CH-3 0 0 1465 Cl H CO(Ph-2-Me)
2-OCH.sub.2CH.sub.2-3 0 0 1466 Cl H CO(Ph-2-Me) 2-cPr, 5-F 0 0 1467
Cl H CO(Ph-2-Me) 2-cPr, 5-Cl 0 0 1468 Cl H CO(Ph-2-Me) 2-cPr, 5-Me
0 0 1469 Cl H CO(Ph-2-Me) 2-OMe, 5-Me 0 0 1470 Cl H CO(Ph-2-Me)
2-F, 6-iPr 0 0 1471 Cl H CO(Ph-2-Me) 2-F, 6-cPr 0 0 1472 Cl H
CO(Ph-2-Me) 2-Cl, 6-Me 0 0 1473 Cl H CO(Ph-2-Me) 2-Cl, 6-cPr 0 0
1474 Cl H CO(Ph-2-Me) 2-Br, 6-Me 0 0 1475 Cl H CO(Ph-2-Me) 2-Br,
6-Et 0 0 1476 Cl H CO(Ph-2-Me) 2-Br, 6-cPr 0 0 1477 Cl H
CO(Ph-2-Me) 2-I, 6-Me 0 0 1478 Cl H CO(Ph-2-Me) 2-I, 6-Et 0 0 1479
Cl H CO(Ph-2-Me) 2,6-Me.sub.2 0 0 1480 Cl H CO(Ph-2-Me) 2-Me, 6-Et
0 0 1481 Cl H CO(Ph-2-Me) 2-Me, 6-cPr 0 0 1482 Cl H CO(Ph-2-Me)
2-Et, 6-cPr 0 0 1483 Cl H CO(Ph-2-Me) 2-iPr, 6-cPr 0 0 1484 Cl H
CO(Ph-2-Me) 2-tBu, 6-cPr 0 0 1485 Cl H CO(Ph-2-Me) 2,6-cPr.sub.2 0
0 1486 Cl H CO(Ph-2-Me) 2-cPr, 6-OMe 0 0 1487 Cl H CO(Ph-2-Me)
2-Br, 3,6-Me.sub.2 0 0 1488 Cl H CO(Ph-2-Me) 2-cPr, 3,5-Me.sub.2 0
0 1489 Cl H CO(Ph-2-Me) 2-cPr, 4, 6-Me.sub.2 0 0 1490 Cl H
CO(Ph-2-Me) 2-Br, 5,6-Me.sub.2 0 0 1491 Cl H CO(Ph-2-Me) 2-cPr,
5,6-Me.sub.2 0 0 1492 Cl H CO(Ph-2-Me) 2-Br, 5-CH.dbd.CH-O-6 0 0
1493 Cl H CO(Ph-2-Me) 2-Me, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1494
Cl H CO(Ph-2-Me) 2-Me, 5-CH.sub.2CH.sub.2O-6 0 0
1495 Cl H CO(Ph-2-Me) 2-Me, 5-CH.dbd.CH--O-6 0 0 1496 Cl H
CO(Ph-2-Me) 2-Et, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1497 Cl H
CO(Ph-2-Me) 2-cPr, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1498 Cl H
CO(Ph-2-Me) 2-cPr, 5-CH.dbd.CH--O-6 0 0 1499 Cl H CO(Ph-2-Me) 2-Br,
3,5,6-Me.sub.3 0 0 1500 Cl H CO(Ph-2-CN) 2-Me 0 0 1501 Cl H
CO(Ph-2-CN) 2-iPr 0 0 1502 Cl H CO(Ph-2-CN) 2-cPr 0 0 1503 Cl H
CO(Ph-2-CN) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1504 Cl H CO(Ph-2-CN)
2,6-Me.sub.2 0 0 1505 Cl H CO(Ph-2-CN) 2-Me, 6-cPr 0 0 1506 Cl H
CO(Ph-2-OMe) 2-Cl 0 0 1507 Cl H CO(Ph-2-OMe) 2-Br 0 0 1508 Cl H
CO(Ph-2-OMe) 2-I 0 0 1509 Cl H CO(Ph-2-OMe) 2-Me 0 0 1510 Cl H
CO(Ph-2-OMe) 2-iPr 0 0 1511 Cl H CO(Ph-2-OMe) 2-cPr 0 0 1512 Cl H
CO(Ph-2-OMe) 2-cBu 0 0 1513 Cl H CO(Ph-2-OMe)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1514 Cl H CO(Ph-2-OMe) 2-cPr, 5-Me
0 0 1515 Cl H CO(Ph-2-OMe) 2-OMe, 5-Me 0 0 1516 Cl H CO(Ph-2-OMe)
2-F, 6-iPr 0 0 1517 Cl H CO(Ph-2-OMe) 2-Cl, 6-cPr 0 0 1518 Cl H
CO(Ph-2-OMe) 2-Br, 6-Me 0 0 1519 Cl H CO(Ph-2-OMe) 2-I, 6-Me 0 0
1520 Cl H CO(Ph-2-OMe) 2,6-Me.sub.2 0 0 1521 Cl H CO(Ph-2-OMe)
2-Me, 6-Et 0 0 1522 Cl H CO(Ph-2-OMe) 2-Me, 6-cPr 0 0 1523 Cl H
CO(Ph-2-OMe) 2,6-cPr.sub.2 0 0 1524 Cl H CO(Ph-2-OMe) 2-cPr,
3,5-Me.sub.2 0 0 1525 Cl H CO(Ph-2-OMe) 2-cPr, 5,6-Me.sub.2 0 0
1526 Cl H CO(Ph-3-Me) 2-Me 0 0 1527 Cl H CO(Ph-3-Me) 2-iPr 0 0 1528
Cl H CO(Ph-3-Me) 2-cPr 0 0 1529 Cl H CO(Ph-3-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1530 Cl H CO(Ph-3-Me) 2,6-Me.sub.2
0 0 1531 Cl H CO(Ph-3-Me) 2-Me, 6-cPr 0 0 1532 Cl H CO(Ph-4-Cl)
2-Me 0 0 1533 Cl H CO(Ph-4-Cl) 2-iPr 0 0 1534 Cl H CO(Ph-4-Cl)
2-cPr 0 0 1535 Cl H CO(Ph-4-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
1536 Cl H CO(Ph-4-Cl) 2,6-Me.sub.2 0 0 1537 Cl H CO(Ph-4-Cl) 2-Me,
6-cPr 0 0 1538 Cl H CO(Ph-4-Br) 2-Me 0 0 1539 Cl H CO(Ph-4-Br)
2-iPr 0 0 1540 Cl H CO(Ph-4-Br) 2-cPr 0 0 1541 Cl H CO(Ph-4-Br)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1542 Cl H CO(Ph-4-Br) 2,6-Me.sub.2
0 0 1543 Cl H CO(Ph-4-Br) 2-Me, 6-cPr 0 0 1544 Cl H CO(Ph-4-I) 2-Me
0 0 1545 Cl H CO(Ph-4-I) 2-iPr 0 0 1546 Cl H CO(Ph-4-I) 2-cPr 0 0
1547 Cl H CO(Ph-4-I) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1548 Cl H
CO(Ph-4-I) 2,6-Me.sub.2 0 0 1549 Cl H CO(Ph-4-I) 2-Me, 6-cPr 0 0
1550 Cl H CO(Ph-4-Me) 2-Cl 0 0 1551 Cl H CO(Ph-4-Me) 2-Br 0 0 1552
Cl H CO(Ph-4-Me) 2-I 0 0 1553 Cl H CO(Ph-4-Me) 2-Me 0 0 1554 Cl H
CO(Ph-4-Me) 2-iPr 0 0 1555 Cl H CO(Ph-4-Me) 2-cPr 0 0 1556 Cl H
CO(Ph-4-Me) 2-cBu 0 0 1557 Cl H CO(Ph-4-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1558 Cl H CO(Ph-4-Me) 2-cPr, 5-Me
0 0 1559 Cl H CO(Ph-4-Me) 2-OMe, 5-Me 0 0 1560 Cl H CO(Ph-4-Me)
2-F, 6-iPr 0 0 1561 Cl H CO(Ph-4-Me) 2-Cl, 6-cPr 0 0 1562 Cl H
CO(Ph-4-Me) 2-Br, 6-Me 0 0 1563 Cl H CO(Ph-4-Me) 2-I, 6-Me 0 0 1564
Cl H CO(Ph-4-Me) 2,6-Me.sub.2 0 0 1565 Cl H CO(Ph-4-Me) 2-Me, 6-Et
0 0 1566 Cl H CO(Ph-4-Me) 2-Me, 6-cPr 0 0 1567 Cl H CO(Ph-4-Me)
2-cPr.sub.2 0 0 1568 Cl H CO(Ph-4-Me) 2-cPr, 3,5-Me.sub.2 0 0 1569
Cl H CO(Ph-4-Me) 2-cPr, 5,6-Me.sub.2 0 0 1570 Cl H CO(Ph-4-tBu)
2-Me 0 0 1571 Cl H CO(Ph-4-tBu) 2-iPr 0 0 1572 Cl H CO(Ph-4-tBu)
2-cPr 0 0 1573 Cl H CO(Ph-4-tBu) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
1574 Cl H CO(Ph-4-tBu) 2,6-Me.sub.2 0 0 1575 Cl H CO(Ph-4-tBu)
2-Me, 6-cPr 0 0 1576 Cl H CO(Ph-4-CO.sub.2Me) 2-Me 0 0 1577 Cl H
CO(Ph-4-CO.sub.2Me) 2-iPr 0 0 1578 Cl H CO(Ph-4-CO.sub.2Me) 2-cPr 0
0 1579 Cl H CO(Ph-4-CO.sub.2Me) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
1580 Cl H CO(Ph-4-CO.sub.2Me) 2,6-Me.sub.2 0 0 1581 Cl H
CO(Ph-4-CO.sub.2Me) 2-Me, 6-cPr 0 0 1582 Cl H CO(Ph-4-COtBu) 2-Me 0
0 1583 Cl H CO(Ph-4-COtBu) 2-iPr 0 0 1584 Cl H CO(Ph-4-COtBu) 2-cPr
0 0 1585 Cl H CO(Ph-4-COtBu) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1586
Cl H CO(Ph-4-COtBu) 2,6-Me.sub.2 0 0 1587 Cl H CO(Ph-4-COtBu) 2-Me,
6-cPr 0 0 1588 Cl H CO(Ph-4-NO.sub.2) 2-Me 0 0 1589 Cl H
CO(Ph-4-NO.sub.2) 2-iPr 0 0 1590 Cl H CO(Ph-4-NO.sub.2) 2-cPr 0 0
1591 Cl H CO(Ph-4-NO.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1592
Cl H CO(Ph-4-NO.sub.2) 2,6-Me.sub.2 0 0 1593 Cl H CO(Ph-4-NO.sub.2)
2-Me, 6-cPr 0 0 1594 Cl H CO(Ph-4-OMe) 2-Me 0 0 1595 Cl H
CO(Ph-4-OMe) 2-iPr 0 0 1596 Cl H CO(Ph-4-OMe) 2-cPr 0 0 1597 Cl H
CO(Ph-4-OMe) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1598 Cl H
CO(Ph-4-OMe) 2,6-Me.sub.2 0 0 1599 Cl H CO(Ph-4-OMe) 2-Me, 6-cPr 0
0 1600 Cl H CO(Ph-2,4-Cl.sub.2) 2-Cl 0 0 1601 Cl H
CO(Ph-2,4-Cl.sub.2) 2-Br 0 0 1602 Cl H CO(Ph-2,4-Cl.sub.2) 2-I 0 0
1603 Cl H CO(Ph-2, 4-Cl.sub.2) 2-Me 0 0 1604 Cl H
CO(Ph-2,4-Cl.sub.2) 2-iPr 0 0 1605 Cl H CO(Ph-2,4-Cl.sub.2) 2-cPr 0
0 1606 Cl H CO(Ph-2,4-Cl.sub.2) 2-cBu 0 0 1607 Cl H
CO(Ph-2,4-Cl.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1608 Cl H
CO(Ph-2,4-Cl.sub.2) 2-cPr, 5-Me 0 0 1609 Cl H CO(Ph-2,4-Cl.sub.2)
2-OMe, 5-Me 0 0 1610 Cl H CO(Ph-2,4-Cl.sub.2) 2-F, 6-iPr 0 0 1611
Cl H CO(Ph-2,4-Cl.sub.2) 2-Cl, 6-cPr 0 0 1612 Cl H
CO(Ph-2,4-Cl.sub.2) 2-Br, 6-Me 0 0 1613 Cl H CO(Ph-2,4-Cl.sub.2)
2-I, 6-Me 0 0 1614 Cl H CO(Ph-2,4-Cl.sub.2) 2,6-Me.sub.2 0 0 1615
Cl H CO(Ph-2,4-Cl.sub.2) 2-Me, 6-Et 0 0 1616 Cl H
CO(Ph-2,4-Cl.sub.2) 2-Me, 6-cPr 0 0 1617 Cl H CO(Ph-2,4-Cl.sub.2)
2,6-cPr.sub.2 0 0 1618 Cl H CO(Ph-2,4-Cl.sub.2) 2-cPr, 3,5-Me.sub.2
0 0 1619 Cl H CO(Ph-2,4-Cl.sub.2) 2-cPr, 5,6-Me.sub.2 0 0 1620 Cl H
CO(Ph-2-CO.sub.2Q.sup.5) 2-Me 0 0 1621 Cl H
CO(Ph-2-CO.sub.2Q.sup.5) 2-iPr 0 0 1622 Cl H
CO(Ph-2-CO.sub.2Q.sup.5) 2-cPr 0 0 1623 Cl H
CO(Ph-2-CO.sub.2Q.sup.5) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1624 Cl H
CO(Ph-2-CO.sub.2Q.sup.5) 2,6-Me.sub.2 0 0 1625 Cl H
CO(Ph-2-CO.sub.2Q.sup.5) 2-Me, 6-cPr 0 0 1626 Cl H
CO(Ph-3-CO.sub.2Q.sup.5) 2-Me 0 0 1627 Cl H
CO(Ph-3-CO.sub.2Q.sup.5) 2-iPr 0 0 1628 Cl H
CO(Ph-3-CO.sub.2Q.sup.5) 2-cPr 0 0 1629 Cl H
CO(Ph-3-CO.sub.2Q.sup.5) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1630 Cl H
CO(Ph-3-CO.sub.2Q.sup.5) 2,6-Me.sub.2 0 0 1631 Cl H
CO(Ph-3-CO.sub.2Q.sup.5) 2-Me, 6-cPr 0 0 1632 Cl H
CO(Ph-4-CO.sub.2Q.sup.5) 2-Me 0 0 1633 Cl H
CO(Ph-4-CO.sub.2Q.sup.5) 2-iPr 0 0 1634 Cl H
CO(Ph-4-CO.sub.2Q.sup.5) 2-cPr 0 0 1635 Cl H
CO(Ph-4-CO.sub.2Q.sup.5) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1636 Cl H
CO(Ph-4-CO.sub.2Q.sup.5) 2,6-Me.sub.2 0 0 1637 Cl H
CO(Ph-4-CO.sub.2Q.sup.5) 2-Me, 6-cPr 0 0 1638 Cl H CO(2-Fur) 2-Me 0
0 1639 Cl H CO(2-Fur) 2-iPr 0 0 1640 Cl H CO(2-Fur) 2-cPr 0 0 1641
Cl H CO(2-Fur) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1642 Cl H CO(2-Fur)
2,6-Me.sub.2 0 0 1643 Cl H CO(2-Fur) 2-Me, 6-cPr 0 0 1644 Cl H
CO(2-Thi) 2-Me 0 0 1645 Cl H CO(2-Thi) 2-iPr 0 0 1646 Cl H
CO(2-Thi) 2-cPr 0 0 1647 Cl H CO(2-Thi)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1648 Cl H CO(2-Thi) 2,6-Me.sub.2 0
0 1649 Cl H CO(2-Thi) 2-Me, 6-cPr 0 0 1650 Cl H CO.sub.2Me 2-F 0 0
1651 Cl H CO.sub.2Me 2-Cl 0 0 1652 Cl H CO.sub.2Me 2-Br 0 0 1653 Cl
H CO.sub.2Me 2-I 0 0 1654 Cl H CO.sub.2Me 2-Me 0 0 1655 Cl H
CO.sub.2Me 2-Et 0 0 1656 Cl H CO.sub.2Me 2-iPr 0 0 1657 Cl H
CO.sub.2Me 2-tBu 0 0 1658 Cl H CO.sub.2Me 2-cPr 0 0 1659 Cl H
CO.sub.2Me 2-(cPr-1-Me) 0 0 1660 Cl H CO.sub.2Me 2-(cPr-2-Me) 0 0
1661 Cl H CO.sub.2Me 2-(cPr-2,2-Cl.sub.2) 0 0 1662 Cl H CO.sub.2Me
2-cBu 0 0 1663 Cl H CO.sub.2Me 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
1664 Cl H CO.sub.2Me 2-CH.dbd.CH--O-3 0 0 1665 Cl H CO.sub.2Me
2-CH.sub.2CH.sub.2O-3 0 0 1666 Cl H CO.sub.2Me 2-OCH.dbd.CH-3 0 0
1667 Cl H CO.sub.2Me 2-OCH.sub.2CH.sub.23 0 0 1668 Cl H CO.sub.2Me
2-cPr, 5-F 0 0 1669 Cl H CO.sub.2Me 2-cPr, 5-Cl 0 0 1670 Cl H
CO.sub.2Me 2-cPr, 5-Me 0 0 1671 Cl H CO.sub.2Me 2-OMe, 5-Me 0 0
1672 Cl H CO.sub.2Me 2-F, 6-iPr 0 0 1673 Cl H CO.sub.2Me 2-F, 6-cPr
0 0 1674 Cl H CO.sub.2Me 2-Cl, 6-Me 0 0 1675 Cl H CO.sub.2Me 2-Cl,
6-cPr 0 0 1676 Cl H CO.sub.2Me 2-Br, 6-Me 0 0 1677 Cl H CO.sub.2Me
2-Br, 6-Et 0 0 1678 Cl H CO.sub.2Me 2-Br, 6-cPr 0 0 1679 Cl H
CO.sub.2Me 2-I, 6-Me 0 0 1680 Cl H CO.sub.2Me 2-I, 6-Et 0 0 1681 Cl
H CO.sub.2Me 2,6-Me.sub.2 0 0 1682 Cl H CO.sub.2Me 2-Me, 6-Et 0 0
1683 Cl H CO.sub.2Me 2-Me, 6-cPr 0 0 1684 Cl H CO.sub.2Me 2-Et,
6-cPr 0 0 1685 Cl H CO.sub.2Me 2-iPr, 6-cPr 0 0 1686 Cl H
CO.sub.2Me 2-tBu, 6-cPr 0 0 1687 Cl H CO.sub.2Me 2,6-cPr.sub.2 0 0
1688 Cl H CO.sub.2Me 2-cPr, 6-OMe 0 0 1689 Cl H CO.sub.2Me 2-Br,
3,6-Me.sub.2 0 0 1690 Cl H CO.sub.2Me 2-cPr, 3,2 0 0 1691 Cl H
CO.sub.2Me 2-cPr, 4,6-Me.sub.2 0 0 1692 Cl H CO.sub.2Me 2-Br,
5,6-Me.sub.2 0 0 1693 Cl H CO.sub.2Me 2-cPr, 5,6-Me.sub.2 0 0 1694
Cl H CO.sub.2Me 2-Br, 5-CH.dbd.CH--O-6 0 0 1695 Cl H CO.sub.2Me
2-Me, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1696 Cl H CO.sub.2Me 2-Me,
5-CH.sub.2CH.sub.2O-6 0 0 1697 Cl H CO.sub.2Me 2-Me,
5-CH.dbd.CH--O-6 0 0 1698 Cl H CO.sub.2Me 2-Et,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1699 Cl H CO.sub.2Me 2-cPr,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1700 Cl H CO.sub.2Me 2-cPr,
5-CH.dbd.CH--O-6 0 0 1701 Cl H CO.sub.2Me 2-Br, 3,5,6-Me.sub.3 0 0
1702 Cl H CO.sub.2Et 2-F 0 0 1703 Cl H CO.sub.2Et 2-Cl 0 0 1704 Cl
H CO.sub.2Et 2-Br 0 0 1705 Cl H CO.sub.2Et 2-I 0 0 1706 Cl H
CO.sub.2Et 2-Me 0 0 1707 Cl H CO.sub.2Et 2-Et 0 0 1708 Cl H
CO.sub.2Et 2-iPr 0 0 1709 Cl H CO.sub.2Et 2-tBu 0 0 1710 Cl H
CO.sub.2Et 2-cPr 0 0 1711 Cl H CO.sub.2Et 2-(cPr-1-Me) 0 0 1712 Cl
H CO.sub.2Et 2-(cPr-2-Me) 0 0 1713 Cl H CO.sub.2Et
2-(cPr-2,2-Cl.sub.2) 0 0 1714 Cl H CO.sub.2Et 2-cBu 0 0 1715 Cl H
CO.sub.2Et 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1716 Cl H CO.sub.2Et
2-CH.dbd.CH--O-3 0 0 1717 Cl H CO.sub.2Et 2-CH.sub.2CH.sub.2O-3 0 0
1718 Cl H CO.sub.2Et 2-OCH.dbd.CH-3 0 0 1719 Cl H CO.sub.2Et
2-OCH.sub.2CH.sub.2-3 0 0 1720 Cl H CO.sub.2Et 2-cPr, 5-F 0 0 1721
Cl H CO.sub.2Et 2-cPr, 5-Cl 0 0 1722 Cl H CO.sub.2Et 2-cPr, 5-Me 0
0 1723 Cl H CO.sub.2Et 2-OMe, 5-Me 0 0 1724 Cl H CO.sub.2Et 2-F,
6-iPr 0 0 1725 Cl H CO.sub.2Et 2-F, 6-cPr 0 0 1726 Cl H CO.sub.2Et
2-Cl, 6-Me 0 0 1727 Cl H CO.sub.2Et 2-Cl, 6-cPr 0 0 1728 Cl H
CO.sub.2Et 2-Br, 6-Me 0 0 1729 Cl H CO.sub.2Et 2-Br, 6-Et 0 0 1730
Cl H CO.sub.2Et 2-Br, 6-cPr 0 0 1731 Cl H CO.sub.2Et 2-I, 6-Me 0 0
1732 Cl H CO.sub.2Et 2-I, 6-Et 0 0 1733 Cl H CO.sub.2Et
2,6-Me.sub.2 0 0 1734 Cl H CO.sub.2Et 2-Me, 6-Et 0 0 1735 Cl H
CO.sub.2Et 2-Me, 6-cPr 0 0 1736 Cl H CO.sub.2Et 2-Et, 6-cPr 0 0
1737 Cl H CO.sub.2Et 2-iPr, 6-cPr 0 0 1738 Cl H CO.sub.2Et 2-tBu,
6-cPr 0 0 1739 Cl H CO.sub.2Et 2,6-cPr.sub.2 0 0 1740 Cl H
CO.sub.2Et 2-cPr, 6-OMe 0 0 1741 Cl H CO.sub.2Et 2-Br, 3,6-Me.sub.2
0 0 1742 Cl H CO.sub.2Et 2-cPr, 3,5-Me.sub.2 0 0 1743 Cl H
CO.sub.2Et 2-cPr, 4,6-Me.sub.2 0 0 1744 Cl H CO.sub.2Et 2-Br,
5,6-Me.sub.2 0 0 1745 Cl H CO.sub.2Et 2-cPr, 5,6-Me.sub.2 0 0
1746 Cl H CO.sub.2Et 2-Br, 5-CH.dbd.CH--O-6 0 0 1747 Cl H
CO.sub.2Et 2-Me, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1748 Cl H
CO.sub.2Et 2-Me, 5-CH.sub.2CH.sub.2O-6 0 0 1749 Cl H CO.sub.2Et
2-Me, 5-CH.dbd.CH--O-6 0 0 1750 Cl H CO.sub.2Et 2-Et,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1751 Cl H CO.sub.2Et 2-cPr,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 1752 Cl H CO.sub.2Et 2-cPr,
5-CH.dbd.CH--O-6 0 0 1753 Cl H CO.sub.2Et 2-Br, 3,5,6-Me.sub.3 0 0
1754 Cl H CO.sub.2iBu 2-Cl 0 0 1755 Cl H CO.sub.2iBu 2-Br 0 0 1756
Cl H CO.sub.2iBu 2-I 0 0 1757 Cl H CO.sub.2iBu 2-Me 0 0 1758 Cl H
CO.sub.2iBu 2-iPr 0 0 1759 Cl H CO.sub.2iBu 2-cPr 0 0 1760 Cl H
CO.sub.2iBu 2-cBu 0 0 1761 Cl H CO.sub.2iBu
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1762 Cl H CO.sub.2iBu 2-cPr, 5-Me
0 0 1763 Cl H CO.sub.2iBu 2-OMe, 5-Me 0 0 1764 Cl H CO.sub.2iBu
2-F, 6-iPr 0 0 1765 Cl H CO.sub.2iBu 2-Cl, 6-cPr 0 0 1766 Cl H
CO.sub.2iBu 2-Br, 6-Me 0 0 1767 Cl H CO.sub.2iBu 2-I, 6-Me 0 0 1768
Cl H CO.sub.2iBu 2,6-Me.sub.2 0 0 1769 Cl H CO.sub.2iBu 2-Me, 6-Et
0 0 1770 Cl H CO.sub.2iBu 2-Me, 6-cPr 0 0 1771 Cl H CO.sub.2iBu
2,6-cPr.sub.2 0 0 1772 Cl H CO.sub.2iBu 2-cPr, 3,5-Me.sub.2 0 0
1773 Cl H CO.sub.2iBu 2-cPr, 5,6-Me.sub.2 0 0 1774 Cl H CO.sub.2Bu
2-Me 0 0 1775 Cl H CO.sub.2Bu 2-iPr 0 0 1776 Cl H CO.sub.2Bu 2-cPr
0 0 1777 Cl H CO.sub.2Bu 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1778 Cl H
CO.sub.2Bu 2,6-Me.sub.2 0 0 1779 Cl H CO.sub.2Bu 2-Me, 6-cPr 0 0
1780 Cl H CO.sub.2CH.sub.2Cl 2-Me 0 0 1781 Cl H CO.sub.2CH.sub.2Cl
2-iPr 0 0 1782 Cl H CO.sub.2CH.sub.2Cl 2-cPr 0 0 1783 Cl H
CO.sub.2CH.sub.2Cl 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1784 Cl H
CO.sub.2CH.sub.2Cl 2,6-Me.sub.2 0 0 1785 Cl H CO.sub.2CH.sub.2Cl
2-Me, 6-cPr 0 0 1786 Cl H CO.sub.2CH.sub.2CCl.sub.3 2-Cl 0 0 1787
Cl H CO.sub.2CH.sub.2CCl.sub.3 2-Br 0 0 1788 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-I 0 0 1789 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-Me 0 0 1790 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-iPr 0 0 1791 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-cPr 0 0 1792 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-cBu 0 0 1793 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1794 Cl
H CO.sub.2CH.sub.2CCl.sub.3 2-cPr, 5-Me 0 0 1795 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-OMe, 5-Me 0 0 1796 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-F, 6-iPr 0 0 1797 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-Cl, 6-cPr 0 0 1798 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-Br, 6-Me 0 0 1799 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-I, 6-Me 0 0 1800 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2,6-Me.sub.2 0 0 1801 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-Me, 6-Et 0 0 1802 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-Me, 6-cPr 0 0 1803 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2,6-cPr.sub.2 0 0 1804 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-cPr, 3,5-Me.sub.2 0 0 1805 Cl H
CO.sub.2CH.sub.2CCl.sub.3 2-cPr, 5,6-Me.sub.2 0 0 1806 Cl H
CO.sub.2CH.sub.2CH.dbd.CH.sub.2 2-Me 0 0 1807 Cl H
CO.sub.2CH.sub.2CH.dbd.CH.sub.2 2-iPr 0 0 1808 Cl H
CO.sub.2CH.sub.2CH.dbd.CH.sub.2 2-cPr 0 0 1809 Cl H
CO.sub.2CH.sub.2CH.dbd.CH.sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0-
1810 Cl H CO.sub.2CH.sub.2CH.dbd.CH.sub.2 2,6-Me.sub.2 0 0 1811 Cl
H CO.sub.2CH.sub.2CH.dbd.CH.sub.2 2-Me, 6-cPr 0 0 1812 Cl H
CO.sub.2CH.sub.2Ph 2-Me 0 0 1813 Cl H CO.sub.2CH.sub.2Ph 2-iPr 0 0
1814 Cl H CO.sub.2CH.sub.2Ph 2-cPr 0 0 1815 Cl H CO.sub.2CH.sub.2Ph
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1816 Cl H CO.sub.2CH.sub.2Ph
2,6-Me.sub.2 0 0 1817 Cl H CO.sub.2CH.sub.2Ph 2-Me, 6-cPr 0 0 1818
Cl H CO.sub.2CH.sub.2CH.sub.2OMe 2-Me 0 0 1819 Cl H
CO.sub.2CH.sub.2CH.sub.2OMe 2-iPr 0 0 1820 Cl H
CO.sub.2CH.sub.2CH.sub.2OMe 2-cPr 0 0 1821 Cl H
CO.sub.2CH.sub.2CH.sub.2OMe 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1822
Cl H CO.sub.2CH.sub.2CH.sub.2OMe 2,6-Me.sub.2 0 0 1823 Cl H
CO.sub.2CH.sub.2CH.sub.2OMe 2-Me, 6-cPr 0 0 1824 Cl H CO.sub.2Ph
2-Cl 0 0 1825 Cl H CO.sub.2Ph 2-Br 0 0 1826 Cl H CO.sub.2Ph 2-I 0 0
1827 Cl H CO.sub.2Ph 2-Me 0 0 1828 Cl H CO.sub.2Ph 2-iPr 0 0 1829
Cl H CO.sub.2Ph 2-cPr 0 0 1830 Cl H CO.sub.2Ph 2-cBu 0 0 1831 Cl H
CO.sub.2Ph 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1832 Cl H CO.sub.2Ph
2-cPr, 5-Me 0 0 1833 Cl H CO.sub.2Ph 2-OMe, 5-Me 0 0 1834 Cl H
CO.sub.2Ph 2-F, 6-iPr 0 0 1835 Cl H CO.sub.2Ph 2-Cl, 6-cPr 0 0 1836
Cl H CO.sub.2Ph 2-Br, 6-Me 0 0 1837 Cl H CO.sub.2Ph 2-I, 6-Me 0 0
1838 Cl H CO.sub.2Ph 2,6-Me.sub.2 0 0 1839 Cl H CO.sub.2Ph 2-Me,
6-Et 0 0 1840 Cl H CO.sub.2Ph 2-Me, 6-cPr 0 0 1841 Cl H CO.sub.2Ph
2,6-cPr.sub.2 0 0 1842 Cl H CO.sub.2Ph 2-cPr, 3,5-Me.sub.2 0 0 1843
Cl H CO.sub.2Ph 2-cPr, 5,6-Me.sub.2 0 0 1844 Cl H CO.sub.2(Ph-4-Cl)
2-Me 0 0 1845 Cl H CO.sub.2(Ph-4-Cl) 2-iPr 0 0 1846 Cl H
CO.sub.2(Ph-4-Cl) 2-cPr 0 0 1847 Cl H CO.sub.2(Ph-4-Cl)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1848 Cl H CO.sub.2(Ph-4-Cl)
2,6-Me.sub.2 0 0 1849 Cl H CO.sub.2(Ph-4-Cl) 2-Me, 6-cPr 0 0 1850
Cl H CO.sub.2 (Ph-4-NO.sub.2) 2-Me 0 0 1851 Cl H CO.sub.2
(Ph-4-NO.sub.2) 2-iPr 0 0 1852 Cl H CO.sub.2 (Ph-4-NO.sub.2) 2-cPr
0 0 1853 Cl H CO.sub.2 (Ph-4-NO.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3
0 0 1854 Cl H CO.sub.2 (Ph-4-NO.sub.2) 2,6-Me.sub.2 0 0 1855 Cl H
CO.sub.2 (Ph-4-NO.sub.2) 2-Me, 6-cPr 0 0 1856 Cl H CO.sub.2 (1-Np)
2-Me 0 0 1857 Cl H CO.sub.2 (1-Np) 2-iPr 0 0 1858 Cl H CO.sub.2
(1-Np) 2-cPr 0 0 1859 Cl H CO.sub.2 (1-Np)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1860 Cl H CO.sub.2 (1-Np)
2,6-Me.sub.2 0 0 1861 Cl H CO.sub.2 (1-Np) 2-Me, 6-cPr 0 0 1862 Cl
H CO.sub.2 (9-Q.sup.4) 2-Me 0 0 1863 Cl H CO.sub.2 (9-Q.sup.4)
2-iPr 0 0 1864 Cl H CO.sub.2 (9-Q.sup.4) 2-cPr 0 0 1865 Cl H
CO.sub.2 (9-Q.sup.4) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1866 Cl H
CO.sub.2 (9-Q.sup.4) 2,6-Me.sub.2 0 0 1867 Cl H CO.sub.2
(9-Q.sup.4) 2-Me, 6-cPr 0 0 1868 Cl H CO.sub.2Q.sup.5 2-Me 0 0 1869
Cl H CO.sub.2Q.sup.5 2-iPr 0 0 1870 Cl H CO.sub.2Q.sup.5 2-cPr 0 0
1871 Cl H CO.sub.2Q.sup.5 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1872 Cl
H CO.sub.2Q.sup.5 2,6-Me.sub.2 0 0 1873 Cl H CO.sub.2Q.sup.5 2-Me,
6-cPr 0 0 1874 Cl H CONMe.sub.2 2-Cl 0 0 1875 Cl H CONMe.sub.2 2-Br
0 0 1876 Cl H CONMe.sub.2 2-I 0 0 1877 Cl H CONMe.sub.2 2-Me 0 0
1878 Cl H CONMe.sub.2 2-iPr 0 0 1879 Cl H CONMe.sub.2 2-cPr 0 0
1880 Cl H CONMe.sub.2 2-cBu 0 0 1881 Cl H CONMe.sub.2 3-CF.sub.3 0
0 1882 Cl H CONMe.sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1883 Cl H
CONMe.sub.2 2-cPr, 5-Me 0 0 1884 Cl H CONMe.sub.2 2-OMe, 5-Me 0 0
1885 Cl H CONMe.sub.2 2-F, 6-iPr 0 0 1886 Cl H CONMe.sub.2 2-Cl,
6-cPr 0 0 1887 Cl H CONMe.sub.2 2-Br, 6-Me 0 0 1888 Cl H
CONMe.sub.2 2-I, 6-Me 0 0 1889 Cl H CONMe.sub.2 2,6-Me.sub.2 0 0
1890 Cl H CONMe.sub.2 2-Me, 6-Et 0 0 1891 Cl H CONMe.sub.2 2-Me,
6-cPr 0 0 1892 Cl H CONMe.sub.2 2,6-cPr.sub.2 0 0 1893 Cl H
CONMe.sub.2 2-cPr, 3,5-Me.sub.2 0 0 1894 Cl H CONMe.sub.2 2-cPr,
5,6-Me.sub.2 0 0 1895 Cl H CONEt.sub.2 2-Cl 0 0 1896 Cl H
CONEt.sub.2 2-Br 0 0 1897 Cl H CONEt.sub.2 2-I 0 0 1898 Cl H
CONEt.sub.2 2-Me 0 0 1899 Cl H CONEt.sub.2 2-iPr 0 0 1900 Cl H
CONEt.sub.2 2-cPr 0 0 1901 Cl H CONEt.sub.2 2-cBu 0 0 1902 Cl H
CONEt.sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1903 Cl H CONEt.sub.2
2-cPr, 5-Me 0 0 1904 Cl H CONEt.sub.2 2-OMe, 5-Me 0 0 1905 Cl H
CONEt.sub.2 2-F, 6-iPr 0 0 1906 Cl H CONEt.sub.2 2-Cl, 6-cPr 0 0
1907 Cl H CONEt.sub.2 2-Br, 6-Me 0 0 1908 Cl H CONEt.sub.2 2-I,
6-Me 0 0 1909 Cl H CONEt.sub.2 2,6-Me.sub.2 0 0 1910 Cl H
CONEt.sub.2 2-Me, 6-Et 0 0 1911 Cl H CONEt.sub.2 2-Me, 6-cPr 0 0
1912 Cl H CONEt.sub.2 2,6-cPr.sub.2 0 0 1913 Cl H CONEt.sub.2
2-cPr, 3,5-Me.sub.2 0 0 1914 Cl H CONEt.sub.2 2-cPr, 5,6-Me.sub.2 0
0 1915 Cl H CON(iPr).sub.2 2-Me 0 0 1916 Cl H CON(iPr).sub.2 2-iPr
0 0 1917 Cl H CON(iPr).sub.2 2-cPr 0 0 1918 Cl H CON(iPr).sub.2
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1919 Cl H CON(iPr).sub.2
2,6-Me.sub.2 0 0 1920 Cl H CON(iPr).sub.2 2-Me, 6-cPr 0 0 1921 Cl H
CO-1-Pyrd 2-Cl 0 0 1922 Cl H CO-1-Pyrd 2-Br 0 0 1923 Cl H CO-1-Pyrd
2-I 0 0 1924 Cl H CO-1-Pyrd 2-Me 0 0 1925 Cl H CO-1-Pyrd 2-iPr 0 0
1926 Cl H CO-1-Pyrd 2-cPr 0 0 1927 Cl H CO-1-Pyrd 2-cBu 0 0 1928 Cl
H CO-1-Pyrd 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1929 Cl H CO-1-Pyrd
2-cPr, 5-Me 0 0 1930 Cl H CO-1-Pyrd 2-OMe, 5-Me 0 0 1931 Cl H
CO-1-Pyrd 2-F, 6-iPr 0 0 1932 Cl H CO-1-Pyrd 2-Cl, 6-cPr 0 0 1933
Cl H CO-1-Pyrd 2-Br, 6-Me 0 0 1934 Cl H CO-1-Pyrd 2-I, 6-Me 0 0
1935 Cl H CO-1-Pyrd 2,6-Me.sub.2 0 0 1936 Cl H CO-1-Pyrd 2-Me, 6-Et
0 0 1937 Cl H CO-1-Pyrd 2-Me, 6-cPr 0 0 1938 Cl H CO-1-Pyrd
2,6-cPr.sub.2 0 0 1939 Cl H CO-1-Pyrd 2-cPr, 3,5-Me.sub.2 0 0 1940
Cl H CO-1-Pyrd 2-cPr, 5,6-Me.sub.2 0 0 1941 Cl H CONMePh 2-Me 0 0
1942 Cl H CONMePh 2-iPr 0 0 1943 Cl H CONMePh 2-cPr 0 0 1944 Cl H
CONMePh 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1945 Cl H CONMePh
2,6-Me.sub.2 0 0 1946 Cl H CONMePh 2-Me, 6-cPr 0 0 1947 Cl H
CONPh.sub.2 2-Me 0 0 1948 Cl H CONPh.sub.2 2-iPr 0 0 1949 Cl H
CONPh.sub.2 2-cPr 0 0 1950 Cl H CONPh.sub.2
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1951 Cl H CONPh.sub.2 2,6-Me.sub.2
0 0 1952 Cl H CONPh.sub.2 2-Me, 6-cPr 0 0 1953 Cl H COSMe 2-Me 0 0
1954 Cl H COSMe 2-iPr 0 0 1955 Cl H COSMe 2-cPr 0 0 1956 Cl H COSMe
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1957 Cl H COSMe 2,6-Me.sub.2 0 0
1958 Cl H COSMe 2-Me, 6-cPr 0 0 1959 Cl H COSC.sub.7H.sub.15 2-Me 0
0 1960 Cl H COSC.sub.7H.sub.15 2-iPr 0 0 1961 Cl H
COSC.sub.7H.sub.15 2-cPr 0 0 1962 Cl H COSC.sub.7H.sub.15
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1963 Cl H COSC.sub.7H.sub.15
2,6-Me.sub.2 0 0 1964 Cl H COSC.sub.7H.sub.15 2-Me, 6-cPr 0 0 1965
Cl H COScHx 2-Me 0 0 1966 Cl H COScHx 2-iPr 0 0 1967 Cl H COScHx
2-cPr 0 0 1968 Cl H COScHx 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1969 Cl
H COScHx 2,6-Me.sub.2 0 0 1970 Cl H COScHx 2-Me, 6-cPr 0 0 1971 Cl
H COSPh 2-Me 0 0 1972 Cl H COSPh 2-iPr 0 0 1973 Cl H COSPh 2-cPr 0
0 1974 Cl H COSPh 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1975 Cl H COSPh
2,6-Me.sub.2 0 0 1976 Cl H COSPh 2-Me, 6-cPr 0 0 1977 Cl H
SO.sub.2Me 2-F 0 0 1978 Cl H SO.sub.2Me 2-Cl 0 0 1979 Cl H
SO.sub.2Me 2-Br 0 0 1980 Cl H SO.sub.2Me 2-I 0 0 1981 Cl H
SO.sub.2Me 2-Me 0 0 1982 Cl H SO.sub.2Me 2-Et 0 0 1983 Cl H
SO.sub.2Me 2-iPr 0 0 1984 Cl H SO.sub.2Me 2-tBu 0 0 1985 Cl H
SO.sub.2Me 2-cPr 0 0 1986 Cl H SO.sub.2Me 2-(cPr-1-Me) 0 0 1987 Cl
H SO.sub.2Me 2-(cPr-2-Me) 0 0 1988 Cl H SO.sub.2Me
2-(cPr-2,2-Cl.sub.2) 0 0 1989 Cl H SO.sub.2Me 2-cBu 0 0 1990 Cl H
SO.sub.2Me 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 1991 Cl H SO.sub.2Me
2-CH.dbd.CH--O-3 0 0 1992 Cl H SO.sub.2Me 2-CH.sub.2CH.sub.2O-3 0 0
1993 Cl H SO.sub.2Me 2-OCH.dbd.CH-3 0 0 1994 Cl H SO.sub.2Me
2OCH.sub.2CH.sub.2-3 0 0 1995 Cl H SO.sub.2Me 2-cPr, 5-F 0 0
1996 Cl H SO.sub.2Me 2-cPr, 5-Cl 0 0 1997 Cl H SO.sub.2Me 2-cPr,
5-Me 0 0 1998 Cl H SO.sub.2Me 2-OMe, 5-Me 0 0 1999 Cl H SO.sub.2Me
2-F, 6-iPr 0 0 2000 Cl H SO.sub.2Me 2-F, 6-cPr 0 0 2001 Cl H
SO.sub.2Me 2-Cl, 6-Me 0 0 2002 Cl H SO.sub.2Me 2-Cl, 6-cPr 0 0 2003
Cl H SO.sub.2Me 2-Br, 6-Me 0 0 2004 Cl H SO.sub.2Me 2-Br, 6-Et 0 0
2005 Cl H SO.sub.2Me 2-Br, 6-cPr 0 0 2006 Cl H SO.sub.2Me 2-I, 6-Me
0 0 2007 Cl H SO.sub.2Me 2-I, 6-Et 0 0 2008 Cl H SO.sub.2Me
2,6-Me.sub.2 0 0 2009 Cl H SO.sub.2Me 2-Me, 6-Et 0 0 2010 Cl H
SO.sub.2Me 2-Me, 6-cPr 0 0 2011 Cl H SO.sub.2Me 2-Et, 6-cPr 0 0
2012 Cl H SO.sub.2Me 2-iPr, 6-cPr 0 0 2013 Cl H SO.sub.2Me 2-tBu,
6-cPr 0 0 2014 Cl H SO.sub.2Me 2,6-cPr.sub.2 0 0 2015 Cl H
SO.sub.2Me 2-cPr, 6-OMe 0 0 2016 Cl H SO.sub.2Me 2-Br, 3,6-Me.sub.2
0 0 2017 Cl H SO.sub.2Me 2-cPr, 3,5-Me.sub.2 0 0 2018 Cl H
SO.sub.2Me 2-cPr, 4, 6-Me.sub.2 0 0 2019 Cl H SO.sub.2Me 2-Br,
5,6-Me.sub.2 0 0 2020 Cl H SO.sub.2Me 2-cPr, 5,6-Me.sub.2 0 0 2021
Cl H SO.sub.2Me 2-Br, 5-CH.dbd.CH--O-6 0 0 2022 Cl H SO.sub.2Me
2-Me, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2023 Cl H SO.sub.2Me 2-Me,
5-CH.sub.2CH.sub.2O-6 0 0 2024 Cl H SO.sub.2Me 2-Me,
5-CH.dbd.CH--O-6 0 0 2025 Cl H SO.sub.2Me 2-Et,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2026 Cl H SO.sub.2Me 2-cPr,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2027 Cl H SO.sub.2Me 2-cPr,
5-CH.dbd.CH--O-6 0 0 2028 Cl H SO.sub.2Me 2-Br, 3,5,6-Me.sub.3 0 0
2029 Cl H SO.sub.2Et 2-Me 0 0 2030 Cl H SO.sub.2Et 2-iPr 0 0 2031
Cl H SO.sub.2Et 2-cPr 0 0 2032 Cl H SO.sub.2Et
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2033 Cl H SO.sub.2Et 2,6-Me.sub.2
0 0 2034 Cl H SO.sub.2Et 2-Me, 6-cPr 0 0 2035 Cl H SO.sub.2Pr 2-Cl
0 0 2036 Cl H SO.sub.2Pr 2-Br 0 0 2037 Cl H SO.sub.2Pr 2-I 0 0 2038
Cl H SO.sub.2Pr 2-Me 0 0 2039 Cl H SO.sub.2Pr 2-iPr 0 0 2040 Cl H
SO.sub.2Pr 2-cPr 0 0 2041 Cl H SO.sub.2Pr 2-cBu 0 0 2042 Cl H
SO.sub.2Pr 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2043 Cl H SO.sub.2Pr
2-cPr, 5-Me 0 0 2044 Cl H SO.sub.2Pr 2-OMe, 5-Me 0 0 2045 Cl H
SO.sub.2Pr 2-F, 6-iPr 0 0 2046 Cl H SO.sub.2Pr 2-Cl, 6-cPr 0 0 2047
Cl H SO.sub.2Pr 2-Br, 6-Me 0 0 2048 Cl H SO.sub.2Pr 2-I, 6-Me 0 0
2049 Cl H SO.sub.2Pr 2,6-Me.sub.2 0 0 2050 Cl H SO.sub.2Pr 2-Me,
6-Et 0 0 2051 Cl H SO.sub.2Pr 2-Me, 6-cPr 0 0 2052 Cl H SO.sub.2Pr
2,6-cPr.sub.2 0 0 2053 Cl H SO.sub.2Pr 2-cPr, 3,5-Me.sub.2 0 0 2054
Cl H SO.sub.2Pr 2-cPr, 5,6-Me.sub.2 0 0 2055 Cl H SO.sub.2iPr 2-Me
0 0 2056 Cl H SO.sub.2iPr 2-iPr 0 0 2057 Cl H SO.sub.2iPr 2-cPr 0 0
2058 Cl H SO.sub.2iPr 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2059 Cl H
SO.sub.2iPr 2,6-Me.sub.2 0 0 2060 Cl H SO.sub.2iPr 2-Me, 6-cPr 0 0
2061 Cl H SO.sub.2C.sub.8H.sub.17 2-Me 0 0 2062 Cl H
SO.sub.2C.sub.8H.sub.17 2-iPr 0 0 2063 Cl H SO.sub.2C.sub.8H.sub.17
2-cPr 0 0 2064 Cl H SO.sub.2C.sub.8H.sub.17
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2065 Cl H SO.sub.2C.sub.8H.sub.17
2,6-Me.sub.2 0 0 2066 Cl H SO.sub.2C.sub.8H.sub.17 2Me, 6-cPr 0 0
2067 Cl H SO.sub.2CH.sub.2Cl 2-Me 0 0 2068 Cl H SO.sub.2CH.sub.2Cl
2-iPr 0 0 2069 Cl H SO.sub.2CH.sub.2Cl 2-cPr 0 0 2070 Cl H
SO.sub.2CH.sub.2Cl 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2071 Cl H
SO.sub.2CH.sub.2Cl 2,6-Me.sub.2 0 0 2072 Cl H SO.sub.2CH.sub.2Cl
2-Me, 6-cPr 0 0 2073 Cl H SO.sub.2CF.sub.3 2-F 0 0 2074 Cl H
SO.sub.2CF.sub.3 2-Cl 0 0 2075 Cl H SO.sub.2CF.sub.3 2-Br 0 0 2076
Cl H SO.sub.2CF.sub.3 2-I 0 0 2077 Cl H SO.sub.2CF.sub.3 2-Me 0 0
2078 Cl H SO.sub.2CF.sub.3 2-Et 0 0 2079 Cl H SO.sub.2CF.sub.3
2-iPr 0 0 2080 Cl H SO.sub.2CF.sub.3 2-tBu 0 0 2081 Cl H
SO.sub.2CF.sub.3 2-cPr 0 0 2082 Cl H SO.sub.2CF.sub.3 2-(cPr-1-Me)
0 0 2083 Cl H SO.sub.2CF.sub.3 2-(cPr-2-Me) 0 0 2084 Cl H
SO.sub.2CF.sub.3 2-(cPr-2,2-Cl.sub.2) 0 0 2085 Cl H
SO.sub.2CF.sub.3 2-cBu 0 0 2086 Cl H SO.sub.2CF.sub.3
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2087 Cl H SO.sub.2CF.sub.3
2-CH.dbd.CH--O-3 0 0 2088 Cl H SO.sub.2CF.sub.3
2-CH.sub.2CH.sub.2O-3 0 0 2089 Cl H SO.sub.2CF.sub.3 2-OCH.dbd.CH-3
0 0 2090 Cl H SO.sub.2CF.sub.3 2-OCH.sub.2CH.sub.2-3 0 0 2091 Cl H
SO.sub.2CF.sub.3 2-cPr, 5-F 0 0 2092 Cl H SO.sub.2CF.sub.3 2-cPr,
5-Cl 0 0 2093 Cl H SO.sub.2CF.sub.3 2-cPr, 5-Me 0 0 2094 Cl H
SO.sub.2CF.sub.3 2-OMe, 5-Me 0 0 2095 Cl H SO.sub.2CF.sub.3 2-F,
6-iPr 0 0 2096 Cl H SO.sub.2CF.sub.3 2-F, 6-cPr 0 0 2097 Cl H
SO.sub.2CF.sub.3 2-Cl, 6-Me 0 0 2098 Cl H SO.sub.2CF.sub.3 2-Cl,
6-cPr 0 0 2099 Cl H SO.sub.2CF.sub.3 2-Br, 6-Me 0 0 2100 Cl H
SO.sub.2CF.sub.3 2-Br, 6-Et 0 0 2101 Cl H SO.sub.2CF.sub.3 2-Br,
6-cPr 0 0 2102 Cl H SO.sub.2CF.sub.3 2-I, 6-Me 0 0 2103 Cl H
SO.sub.2CF.sub.3 2-I, 6-Et 0 0 2104 Cl H SO.sub.2CF.sub.3
2,6-Me.sub.2 0 0 2105 Cl H SO.sub.2CF.sub.3 2-Me, 6-Et 0 0 2106 Cl
H SO.sub.2CF.sub.3 2-Me, 6-cPr 0 0 2107 Cl H SO.sub.2CF.sub.3 2-Et,
6-cPr 0 0 2108 Cl H SO.sub.2CF.sub.3 2-iPr, 6-cPr 0 0 2109 Cl H
SO.sub.2CF.sub.3 2-tBu, 6-cPr 0 0 2110 Cl H SO.sub.2CF.sub.3
2,6-cPr.sub.2 0 0 2111 Cl H SO.sub.2CF.sub.3 2-cPr, 6-OMe 0 0 2112
Cl H SO.sub.2CF.sub.3 2-Br, 3,6-Me.sub.2 0 0 2113 Cl H
SO.sub.2CF.sub.3 2-cPr, 3,5-Me.sub.2 0 0 2114 Cl H SO.sub.2CF.sub.3
2-cPr, 4, 6-Me.sub.2 0 0 2115 Cl H SO.sub.2CF.sub.3 2-Br,
5,6-Me.sub.2 0 0 2116 Cl H SO.sub.2CF.sub.3 2-cPr, 5,6-Me.sub.2 0 0
2117 Cl H SO.sub.2CF.sub.3 2-Br, 5-CH.dbd.CH--O-6 0 0 2118 Cl H
SO.sub.2CF.sub.3 2-Me, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2119 Cl H
SO.sub.2CF.sub.3 2-Me, 5-CH.sub.2CH.sub.2O-6 0 0 2120 Cl H
SO.sub.2CF.sub.3 2-Me, 5-CH.dbd.CH--O-6 0 0 2121 Cl H
SO.sub.2CF.sub.3 2-Et, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2122 Cl H
SO.sub.2CF.sub.3 2-cPr, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2123 Cl H
SO.sub.2CF.sub.3 2-cPr, 5-CH.dbd.CH--O-6 0 0 2124 Cl H
SO.sub.2CF.sub.3 2-Br, 3,5,6-Me.sub.3 0 0 2125 Cl H
SO.sub.2CCl.sub.3 2-Me 0 0 2126 Cl H SO.sub.2CCl.sub.3 2-iPr 0 0
2127 Cl H SO.sub.2CCl.sub.3 2-cPr 0 0 2128 Cl H SO.sub.2CCl.sub.3
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2129 Cl H SO.sub.2CCl.sub.3
2,6-Me.sub.2 0 0 2130 Cl H SO.sub.2CCl.sub.3 2-Me, 6-cPr 0 0 2131
Cl H SO.sub.2CH.sub.2CF.sub.3 2-Me 0 0 2132 Cl H
SO.sub.2CH.sub.2CF.sub.3 2-iPr 0 0 2133 Cl H
SO.sub.2CH.sub.2CF.sub.3 2-cPr 0 0 2134 Cl H
SO.sub.2CH.sub.2CF.sub.3 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2135 Cl H
SO.sub.2CH.sub.2CF.sub.3 2,6-Me.sub.2 0 0 2136 Cl H
SO.sub.2CH.sub.2CF.sub.3 2-Me, 6-cPr 0 0 2137 Cl H
SO.sub.2CH.sub.2CH.sub.2CH.sub.2Cl 2-Me 0 0 2138 Cl H
SO.sub.2CH.sub.2CH.sub.2CH.sub.2Cl 2-iPr 0 0 2139 Cl H
SO.sub.2CH.sub.2CH.sub.2CH.sub.2Cl 2-cPr 0 0 2140 Cl H
SO.sub.2CH.sub.2CH.sub.2CH.sub.2Cl 2-CH.sub.2CH.sub.2CH.sub.2-3 - 0
0 2141 Cl H SO.sub.2CH.sub.2CH.sub.2CH.sub.2Cl 2,6-Me.sub.2 0 0
2142 Cl H SO.sub.2CH.sub.2CH.sub.2CH.sub.2Cl 2-Me, 6-cPr 0 0 2143
Cl H SO.sub.2Ph 2-F 0 0 2144 Cl H SO.sub.2Ph 2-Cl 0 0 2145 Cl H
SO.sub.2Ph 2-Br 0 0 2146 Cl H SO.sub.2Ph 2-I 0 0 2147 Cl H
SO.sub.2Ph 2-Me 0 0 2148 Cl H SO.sub.2Ph 2-Et 0 0 2149 Cl H
SO.sub.2Ph 2-iPr 0 0 2150 Cl H SO.sub.2Ph 2-tBu 0 0 2151 Cl H
SO.sub.2Ph 2-cPr 0 0 2152 Cl H SO.sub.2Ph 2-(cPr-1-Me) 0 0 2153 Cl
H SO.sub.2Ph 2-(cPr-2-Me) 0 0 2154 Cl H SO.sub.2Ph
2-(cPr-2,2-Cl.sub.2) 0 0 2155 Cl H SO.sub.2Ph 2-cBu 0 0 2156 Cl H
SO.sub.2Ph 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2157 Cl H SO.sub.2Ph
2-CH.dbd.CHO-3 0 0 2158 Cl H SO.sub.2Ph 2-CH.sub.2CH.sub.2O-3 0 0
2159 Cl H SO.sub.2Ph 2-OCH.dbd.CH-3 0 0 2160 Cl H SO.sub.2Ph
2-OCH.sub.2CH.sub.2-3 0 0 2161 Cl H SO.sub.2Ph 2-cPr, 5-F 0 0 2162
Cl H SO.sub.2Ph 2-cPr, 5-Cl 0 0 2163 Cl H SO.sub.2Ph 2-cPr, 5-Me 0
0 2164 Cl H SO.sub.2Ph 2-OMe, 5-Me 0 0 2165 Cl H SO.sub.2Ph 2-F,
6-iPr 0 0 2166 Cl H SO.sub.2Ph 2-F, 6-cPr 0 0 2167 Cl H SO.sub.2Ph
2-Cl, 6-Me 0 0 2168 Cl H SO.sub.2Ph 2-Cl, 6-cPr 0 0 2169 Cl H
SO.sub.2Ph 2-Br, 6-Me 0 0 2170 Cl H SO.sub.2Ph 2-Br, 6-Et 0 0 2171
Cl H SO.sub.2Ph 2-Br, 6-cPr 0 0 2172 Cl H SO.sub.2Ph 2-I, 6-Me 0 0
2173 Cl H SO.sub.2Ph 2-I, 6-Et 0 0 2174 Cl H SO.sub.2Ph
2,6-Me.sub.2 0 0 2175 Cl H SO.sub.2Ph 2-Me, 6-Et 0 0 2176 Cl H
SO.sub.2Ph 2-Me, 6-cPr 0 0 2177 Cl H SO.sub.2Ph 2-Et, 6-cPr 0 0
2178 Cl H SO.sub.2Ph 2-iPr, 6-cPr 0 0 2179 Cl H SO.sub.2Ph 2-tBu,
6-cPr 0 0 2180 Cl H SO.sub.2Ph 2,6-cPr.sub.2 0 0 2181 Cl H
SO.sub.2Ph 2-cPr, 6-OMe 0 0 2182 Cl H SO.sub.2Ph 2-Br, 3,6-Me.sub.2
0 0 2183 Cl H SO.sub.2Ph 2-cPr, 3,5-Me.sub.2 0 0 2184 Cl H
SO.sub.2Ph 2-cPr, 4, 6-Me.sub.2 0 0 2185 Cl H SO.sub.2Ph 2-Br,
5,6-Me.sub.2 0 0 2186 Cl H SO.sub.2Ph 2-cPr, 5,6-Me.sub.2 0 0 2187
Cl H SO.sub.2Ph 2-Br, 5-CH.dbd.CH--O-6 0 0 2188 Cl H SO.sub.2Ph
2-Me, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2189 Cl H SO.sub.2Ph 2-Me,
5-CH.sub.2CH.sub.2O-6 0 0 2190 Cl H SO.sub.2Ph 2-Me,
5-CH.dbd.CH--O-6 0 0 2191 Cl H SO.sub.2Ph 2-Et,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2192 Cl H SO.sub.2Ph 2-cPr,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2193 Cl H SO.sub.2Ph 2-cPr,
5-CH.dbd.CH--O-6 0 0 2194 Cl H SO.sub.2Ph 2-Br, 3,5,6-Me.sub.3 0 0
2195 Cl H SO.sub.2 (Ph-4-Cl) 2-Cl 0 0 2196 Cl H SO.sub.2 (Ph-4-Cl)
2-Br 0 0 2197 Cl H SO.sub.2 (Ph-4-cl) 2-I 0 0 2198 Cl H SO.sub.2
(Ph-4-Cl) 2-Me 0 0 2199 Cl H SO.sub.2 (Ph-4-Cl) 2-iPr 0 0 2200 Cl H
SO.sub.2 (Ph-4-Cl) 2-tBu 0 0 2201 Cl H SO.sub.2 (Ph-4-Cl) 2-cPr 0 0
2202 Cl H SO.sub.2 (Ph-4-Cl) 2-cBu 0 0 2203 Cl H SO.sub.2 (Ph-4-Cl)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2204 Cl H SO.sub.2 (Ph-4-Cl)
2-cPr, 5-Me 0 0 2205 Cl H SO.sub.2 (Ph-4-Cl) 2-OMe, 5-Me 0 0 2206
Cl H SO.sub.2 (Ph-4-Cl) 2-F, 6-iPr 0 0 2207 Cl H SO.sub.2 (Ph-4-Cl)
2-Cl, 6-cPr 0 0 2208 Cl H SO.sub.2 (Ph-4-Cl) 2-Br, 6-Me 0 0 2209 Cl
H SO.sub.2 (Ph-4-Cl) 2-I, 6-Me 0 0 2210 Cl H SO.sub.2 (Ph-4-Cl)
2,6-Me.sub.2 0 0 2211 Cl H SO.sub.2 (Ph-4-Cl) 2-Me, 6-Et 0 0 2212
Cl H SO.sub.2 (Ph-4-Cl) 2-Me, 6-cPr 0 0 2213 Cl H SO.sub.2
(Ph-4-Cl) 2,6-cPr.sub.2 0 0 2214 Cl H SO.sub.2 (Ph-4-Cl) 2-cPr,
3,5-Me.sub.2 0 0 2215 Cl H SO.sub.2 (Ph-4-Cl) 2-cPr, 5,6-Me.sub.2 0
0 2216 Cl H SO.sub.2 (Ph-4-Me) 2-F 0 0 2217 Cl H SO.sub.2 (Ph-4-Me)
2-Cl 0 0 2218 Cl H SO.sub.2 (Ph-4-Me) 2-Br 0 0 2219 Cl H SO.sub.2
(Ph-4-Me) 2-I 0 0 2220 Cl H SO.sub.2 (Ph-4-Me) 2-Me 0 0 2221 Cl H
SO.sub.2 (Ph-4-Me) 2-Et 0 0 2222 Cl H SO.sub.2 (Ph-4-Me) 2-iPr 0 0
2223 Cl H SO.sub.2 (Ph-4-Me) 2-sBu 0 0 2224 Cl H SO.sub.2 (Ph-4-Me)
2-tBu 0 0 2225 Cl H SO.sub.2 (Ph-4-Me) 2-cPr 0 0 2226 Cl H SO.sub.2
(Ph-4-Me) 2-(cPr-1-Me) 0 0 2227 Cl H SO.sub.2 (Ph-4-Me)
2-(cPr-2-Me) 0 0 2228 Cl H SO.sub.2 (Ph-4-Me) 2-(cPr-2,2-Cl.sub.2)
0 0 2229 Cl H SO.sub.2 (Ph-4-Me) 2-cBu 0 0 2230 Cl H SO.sub.2
(Ph-4-Me) 2-cHx 0 0 2231 Cl H SO.sub.2 (Ph-4-Me) 2-Ph 0 0 2232 Cl H
SO.sub.2 (Ph-4-Me) 2-OMe 0 0 2233 Cl H SO.sub.2 (Ph-4-Me)
2-OSO.sub.2 (Ph-4-Me) 0 0 2234 Cl H SO.sub.2 (Ph-4-Me) 3-Cl 0 0
2235 Cl H SO.sub.2 (Ph-4-Me) 3-tBu 0 0 2236 Cl H SO.sub.2 (Ph-4-Me)
3-CF.sub.3 0 0 2237 Cl H SO.sub.2 (Ph-4-Me) 3-CN 0 0 2238 Cl H
SO.sub.2 (Ph-4-Me) 3-OMe 0 0 2239 Cl H SO.sub.2 (Ph-4-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2240 Cl H SO.sub.2 (Ph-4-Me)
2-CH.dbd.CH.dbd.CH.dbd.CH-3 0 0 2241 Cl H SO.sub.2 (Ph-4-Me)
2-CH.dbd.CH--O-3 0 0 2242 Cl H SO.sub.2 (Ph-4-Me)
2-CH.sub.2CH.sub.2O-3 0 0 2243 Cl H SO.sub.2 (Ph-4-Me)
2-OCH.dbd.CH-3 0 0 2244 Cl H SO.sub.2 (Ph-4-Me)
2-OCH.sub.2CH.sub.2-3 0 0 2245 Cl H SO.sub.2 (Ph-4-Me) 2-Br, 4-tBu
0 0
2246 Cl H SO.sub.2 (Ph-4-Me) 2-Me, 4-Cl 0 0 2247 Cl H SO.sub.2
(Ph-4-Me) 2, 4-Me.sub.2 0 0 2248 Cl H SO.sub.2 (Ph-4-Me) 2-iPr,
4-Br 0 0 2249 Cl H SO.sub.2 (Ph-4-Me) 2-iPr, 5-Me 0 0 2250 Cl H
SO.sub.2 (Ph-4-Me) 2-cPr, 5-F 0 0 2251 Cl H SO.sub.2 (Ph-4-Me)
2-cPr, 5-Cl 0 0 2252 Cl H SO.sub.2 (Ph-4-Me) 2-cPr, 5-Me 0 0 2253
Cl H SO.sub.2 (Ph-4-Me) 2-OMe, 5-Me 0 0 2254 Cl H SO.sub.2
(Ph-4-Me) 2-F, 6-iPr 0 0 2255 Cl H SO.sub.2 (Ph-4-Me) 2-F, 6-cPr 0
0 2256 Cl H SO.sub.2 (Ph-4-Me) 2-Cl, 6-Me 0 0 2257 Cl H SO.sub.2
(Ph-4-Me) 2-Cl, 6-cPr 0 0 2258 Cl H SO.sub.2 (Ph-4-Me) 2-Br, 6-Me 0
0 2259 Cl H SO.sub.2 (Ph-4-Me) 2-Br, 6-Et 0 0 2260 Cl H SO.sub.2
(Ph-4-Me) 2-Br, 6-cPr 0 0 2261 Cl H SO.sub.2 (Ph-4-Me) 2-I, 6-Me 0
0 2262 Cl H SO.sub.2 (Ph-4-Me) 2-I, 6-Et 0 0 2263 Cl H SO.sub.2
(Ph-4-Me) 2,6-Me.sub.2 0 0 2264 Cl H SO.sub.2 (Ph-4-Me) 2-Me, 6-Et
0 0 2265 Cl H SO.sub.2 (Ph-4-Me) 2-Me, 6-cPr 0 0 2266 Cl H SO.sub.2
(Ph-4-Me) 2-Et, 6-cPr 0 0 2267 Cl H SO.sub.2 (Ph-4-Me) 2-iPr, 6-cPr
0 0 2268 Cl H SO.sub.2 (Ph-4-Me) 2-tBu, 6-cPr 0 0 2269 Cl H
SO.sub.2 (Ph-4-Me) 2,6-cPr.sub.2 0 0 2270 Cl H SO.sub.2 (Ph-4-Me)
2-cPr, 6-OMe 0 0 2271 Cl H SO.sub.2 (Ph-4-Me) 2-Br, 3,6-Me.sub.2 0
0 2272 Cl H SO.sub.2 (Ph-4-Me) 2-cPr, 3,5-Me.sub.2 0 0 2273 Cl H
SO.sub.2 (Ph-4-Me) 2-cPr, 4, 6-Me.sub.2 0 0 2274 Cl H SO.sub.2
(Ph-4-Me) 2-Br, 5,6-Me.sub.2 0 0 2275 Cl H SO.sub.2 (Ph-4-Me)
2-cPr, 5,6-Me.sub.2 0 0 2276 Cl H SO.sub.2 (Ph-4-Me) 2-Br,
5-CH.dbd.CH--O-6 0 0 2277 Cl H SO.sub.2 (Ph-4-Me) 2-Me,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2278 Cl H SO.sub.2 (Ph-4-Me) 2-Me,
5-CH.sub.2CH.sub.2O-6 0 0 2279 Cl H SO.sub.2 (Ph-4-Me) 2-Me,
5-CH.dbd.CH--O-6 0 0 2280 Cl H SO.sub.2 (Ph-4-Me) 2-Et,
5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2281 Cl H SO.sub.2 (Ph-4-Me)
2-cPr, 5-CH.sub.2CH.sub.2CH.sub.2-6 0 0 2282 Cl H SO.sub.2
(Ph-4-Me) 2-cPr, 5-CH.dbd.CH--O-6 0 0 2283 Cl H SO.sub.2 (Ph-4-Me)
2-Br, 3,5,6-Me.sub.3 0 0 2284 Cl H SO.sub.2 (Ph-4-No2) 2-Cl 0 0
2285 Cl H SO.sub.2 (Ph-4-NO.sub.2) 2-Br 0 0 2286 Cl H SO.sub.2
(Ph-4-NO.sub.2) 2-I 0 0 2287 Cl H SO.sub.2 (Ph-4-NO.sub.2) 2-Me 0 0
2288 Cl H SO.sub.2 (Ph-4-NO.sub.2) 2-iPr 0 0 2289 Cl H SO.sub.2
(Ph-4-NO.sub.2) 2-cPr 0 0 2290 Cl H SO.sub.2 (Ph-4-NO.sub.2) 2-cBu
0 0 2291 Cl H SO.sub.2 (Ph-4-NO.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3
0 0 2292 Cl H SO.sub.2 (Ph-4-NO.sub.2) 2-cPr, 5-Me 0 0 2293 Cl H
SO.sub.2 (Ph-4-NO.sub.2) 2-OMe, 5-Me 0 0 2294 Cl H SO.sub.2
(Ph-4-NO.sub.2) 2-F, 6-iPr 0 0 2295 Cl H SO.sub.2 (Ph-4-NO.sub.2)
2-Cl, 6-cPr 0 0 2296 Cl H SO.sub.2 (Ph-4-NO2) 2-Br, 6-Me 0 0 2297
Cl H SO.sub.2 (Ph-4-NO.sub.2) 2-I, 6-Me 0 0 2298 Cl H SO.sub.2
(Ph-4-NO.sub.2) 2,6-Me.sub.2 0 0 2299 Cl H SO.sub.2 (Ph-4-NO.sub.2)
2-Me, 6-Et 0 0 2300 Cl H SO.sub.2 (Ph-4-NO.sub.2) 2-Me, 6-cPr 0 0
2301 Cl H SO.sub.2 (Ph-4-NO.sub.2) 2,6-cPr.sub.2 0 0 2302 Cl H
SO.sub.2 (Ph-4-NO.sub.2) 2-cPr, 3,5-Me.sub.2 0 0 2303 Cl H SO.sub.2
(Ph-4-NO.sub.2) 2-cPr, 5,6-Me.sub.2 0 0 2304 Cl H SO.sub.2
(Ph-4-OMe) 2-Me 0 0 2305 Cl H SO.sub.2 (Ph-4-OMe) 2-iPr 0 0 2306 Cl
H SO.sub.2 (Ph-4-OMe) 2-cPr 0 0 2307 Cl H SO.sub.2 (Ph-4-OMe)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2308 Cl H SO.sub.2 (Ph-4-OMe)
2,6-Me.sub.2 0 0 2309 Cl H SO.sub.2 (Ph-4-OMe) 2-Me, 6-cPr 0 0 2310
Cl H SO.sub.2 (Ph-2,4,6-Me.sub.3) 2-Me 0 0 2311 Cl H SO.sub.2
(Ph-2,4,6-Me.sub.3) 2-iPr 0 0 2312 Cl H SO.sub.2
(Ph-2,4,6-Me.sub.3) 2-cPr 0 0 2313 Cl H SO.sub.2
(Ph-2,4,6-Me.sub.3) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2314 Cl H
SO.sub.2 (Ph-2,4,6-Me.sub.3) 2,6-Me.sub.2 0 0 2315 Cl H SO.sub.2
(Ph-2,4,6-Me.sub.3) 2-Me, 6-cPr 0 0 2316 Cl H SO.sub.2
(Ph-2,4,6-iPr.sub.3) 2-Me 0 0 2317 Cl H SO.sub.2
(Ph-2,4,6-iPr.sub.3) 2-iPr 0 0 2318 Cl H SO.sub.2
(Ph-2,4,6-iPr.sub.3) 2-cPr 0 0 2319 Cl H SO.sub.2
(Ph-2,4,6-iPr.sub.3) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2320 Cl H
SO.sub.2 (Ph-2,4,6-iPr.sub.3) 2,6-Me.sub.2 0 0 2321 Cl H SO.sub.2
(Ph-2,4,6-iPr.sub.3) 2-Me, 6-cPr 0 0 2322 Cl H SO.sub.2
(Ph-2-SO.sub.2OQ.sup.5) 2-Me 0 0 2323 Cl H SO.sub.2
(Ph-2-SO.sub.2OQ.sup.5) 2-iPr 0 0 2324 Cl H SO.sub.2
(Ph-2-SO.sub.2OQ.sup.5) 2-cPr 0 0 2325 Cl H SO.sub.2
(Ph-2-SO.sub.2OQ.sup.5) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2326 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.5) 2,6-Me.sub.2 0 0 2327 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.5) 2-Me, 6-cPr 0 0 2328 Cl H SO.sub.2
(Ph-3-SO.sub.2OQ.sup.5) 2-Me 0 0 2329 Cl H SO.sub.2
(Ph-3-SO.sub.2OQ.sup.5) 2-iPr 0 0 2330 Cl H SO.sub.2
(Ph-3-SO.sub.2OQ.sup.5) 2-cPr 0 0 2331 Cl H SO.sub.2
(Ph-3-SO.sub.2OQ.sup.5) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2332 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.5) 2,6-Me.sub.2 0 0 2333 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.5) 2-Me, 6-cPr 0 0 2334 Cl H SO.sub.2
(Ph-4-SO.sub.2OQ.sup.5) 2-Me 0 0 2335 Cl H SO.sub.2
(Ph-4-SO.sub.2OQ.sup.5) 2-iPr 0 0 2336 Cl H SO.sub.2
(Ph-4-SO.sub.2OQ.sup.5) 2-cPr 0 0 2337 Cl H SO.sub.2
(Ph-4-SO.sub.2OQ.sup.5) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2338 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.5) 2,6-Me.sub.2 0 0 2339 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.5) 2-Me, 6-cPr 0 0 2340 Cl H
SO.sub.2OQ.sup.5 2-Me 0 0 2341 Cl H SO.sub.2OQ.sup.5 2-iPr 0 0 2342
Cl H SO.sub.2OQ.sup.5 2-cPr 0 0 2343 Cl H SO.sub.2OQ.sup.5
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2344 Cl H SO.sub.2OQ.sup.5
2,6-Me.sub.2 0 0 2345 Cl H SO.sub.2OQ.sup.5 2-Me, 6-cPr 0 0 2346 Cl
H SO.sub.2NMe.sub.2 2-Cl 0 0 2347 Cl H SO.sub.2NMe.sub.2 2-Br 0 0
2348 Cl H SO.sub.2NMe.sub.2 2-I 0 0 2349 Cl H SO.sub.2NMe.sub.2
2-Me 0 0 2350 Cl H SO.sub.2NMe.sub.2 2-iPr 0 0 2351 Cl H
SO.sub.2NMe.sub.2 2-cPr 0 0 2352 Cl H SO.sub.2NMe.sub.2 2-cBu 0 0
2353 Cl H SO.sub.2NMe.sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2354
Cl H SO.sub.2NMe.sub.2 2-cPr, 5-Me 0 0 2355 Cl H SO.sub.2NMe.sub.2
2-OMe, 5-Me 0 0 2356 Cl H SO.sub.2NMe.sub.2 2-F, 6-iPr 0 0 2357 Cl
H SO.sub.2NMe.sub.2 2-Cl, 6-cPr 0 0 2358 Cl H SO.sub.2NMe.sub.2
2-Br, 6-Me 0 0 2359 Cl H SO.sub.2NMe.sub.2 2-I, 6-Me 0 0 2360 Cl H
SO.sub.2NMe.sub.2 2,6-Me.sub.2 0 0 2361 Cl H SO.sub.2NMe.sub.2
2-Me, 6-Et 0 0 2362 Cl H SO.sub.2NMe.sub.2 2-Me, 6-cPr 0 0 2363 Cl
H SO.sub.2NMe.sub.2 2,6-cPr.sub.2 0 0 2364 Cl H SO.sub.2NMe.sub.2
2-cPr, 3,5-Me.sub.2 0 0 2365 Cl H SO.sub.2NMe 2-cPr, 5,6-Me.sub.2 0
0 2366 Cl H SO.sub.2OEt 2-Me 0 0 2367 Cl H SO.sub.2OEt 2-iPr 0 0
2368 Cl H SO.sub.2OEt 2-cPr 0 0 2369 Cl H SO.sub.2OEt
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2370 Cl H SO.sub.2OEt 2,6-Me.sub.2
0 0 2371 Cl H SO.sub.2OEt 2-Me, 6-cPr 0 0 2372 Cl Me H 2-Me 0 0
2373 Cl Me H 2-iPr 0 0 2374 Cl Me H 2-cPr 0 0 2375 Cl Me H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2376 Cl Me H 2,6-Me.sub.2 0 0 2377
Cl Me H 2-Me, 6-cPr 0 0 2378 Cl CH.sub.2OMe H 2-Me 0 0 2379 Cl
CH.sub.2OMe H 2-iPr 0 0 2380 Cl CH.sub.2OMe H 2-cPr 0 0 2381 Cl
CH.sub.2OMe H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2382 Cl CH.sub.2OMe
H 2,6-Me.sub.2 0 0 2383 Cl CH.sub.2OMe H 2-Me, 6-cPr 0 0 2384 Cl
CO.sub.2Et H 2-Me 0 0 2385 Cl CO.sub.2Et H 2-iPr 0 0 2386 Cl
CO.sub.2Et H 2-tBu 0 0 2387 Cl CO.sub.2Et H 2-cPr 0 0 2388 Cl
CO.sub.2Et H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2389 Cl CO.sub.2Et H
2,6-Me.sub.2 0 0 2390 Cl CO.sub.2Et H 2-Me, 6-cPr 0 0 2391 Cl
CO(Ph-2-F) H 2-tBu 0 0 2392 Cl OMe H 2-Me 0 0 2393 Cl
O(Ph-2,4-F.sub.2) H 2,4-F.sub.2 0 0 2394 Cl O(Ph-2,6-F.sub.2) H
2,6-F.sub.2 0 0 2395 Cl O(Ph-2-Me) H 2-Me 0 0 2396 Cl O(Ph-2-Me) H
2-iPr 0 0 2397 Cl O(Ph-2-Me) H 2-cPr 0 0 2398 Cl O(Ph-2-Me) H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2399 Cl O(Ph-2-Me) H 2,6-Me.sub.2
0 0 2400 Cl O(Ph-2-Me) H 2-Me, 6-cPr 0 0 2401 Cl SPh H 2-Me 0 0
2402 Cl SiMe.sub.3 H H 0 0 2403 Cl SiMe.sub.3 H 2-Me 0 0 2404 Cl
SiMe.sub.3 H 2-iPr 0 0 2405 Cl SiMe.sub.3 H 2-tBu 0 0 2406 Cl
SiMe.sub.3 H 2-cPr 0 0 2407 Cl SiMe.sub.3 H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2408 Cl SiMe.sub.3 H 2,6-Me.sub.2
0 0 2409 Cl SiMe.sub.3 H 2-Me, 6-cPr 0 0 2410 Br H H 2-Cl 0 0 2411
Br H H 2-Me 0 0 2412 Br H H 2-iPr 0 0 2413 Br H H 2-cPr 0 0 2414 Br
H H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2415 Br H H 2,6-Me.sub.2 0 0
2416 Br H H 2-Me, 6-cPr 0 0 2417 Me H H 2-Me 0 0 2418 Me H H 2-iPr
0 0 2419 Me H H 2-cPr 0 0 2420 Me H H 2-CH.sub.2CH.sub.2CH.sub.2-3
0 0 2421 Me H H 2,6-Me.sub.2 0 0 2422 Me H H 2-Me, 6-cPr 0 0 2423
cPr H H 2-Me 0 0 2424 cPr H H 2-iPr 0 0 2425 cPr H H 2-cPr 0 0 2426
cPr H H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2427 cPr H H 2,6-Me.sub.2
0 0 2428 cPr H H 2-Me, 6-cPr 0 0 2429 CF.sub.3 H H 2-Cl 0 0 2430
CF.sub.3 H H 2-Me 0 0 2431 CF.sub.3 H H 2-iPr 0 0 2432 CF.sub.3 H H
2-cPr 0 0 2433 CF.sub.3 H H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2434
CF.sub.3 H H 2,6-Me.sub.2 0 0 2435 CF.sub.3 H H 2-Me, 6-cPr 0 0
2436 CH.dbd.CH.sub.2 H H 2-Me 0 0 2437 CH.dbd.CH.sub.2 H H 2-iPr 0
0 2438 CH.dbd.CH.sub.2 H H 2-cPr 0 0 2439 CH.dbd.CH.sub.2 H H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2440 CH.dbd.CH.sub.2 H H
2,6-Me.sub.2 0 0 2441 CH.dbd.CH.sub.2 H H 2-Me, 6-cPr 0 0 2442
CH.dbd.CHMe H H 2-Me 0 0 2443 CH.dbd.CHMe H H 2-iPr 0 0 2444
CH.dbd.CHMe H H 2-cPr 0 0 2445 CH.dbd.CHMe H H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2446 CH.dbd.CHMe H H 2,6-Me.sub.2
0 0 2447 CH.dbd.CHMe H H 2-Me, 6-cPr 0 0 2448
CH.sub.2CH.dbd.CH.sub.2 H H 2-Me 0 0 2449 CN H H 2-Me 0 0 2450 CN H
H 2-iPr 0 0 2451 CN H H 2-cPr 0 0 2452 CN H H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2453 CN H H 2,6-Me.sub.2 0 0 2454
CN H H 2-Me, 6-cPr 0 0 2455 COMe H H 2-Me 0 0 2456 COMe H H 2-iPr 0
0 2457 COMe H H 2-cPr 0 0 2458 COMe H H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2459 COMe H H 2,6-Me.sub.2 0 0
2460 COMe H H 2-Me, 6-cPr 0 0 2461 COBu H H 2,6-Me.sub.2 0 0 2462
CONMe.sub.2 H H 2,6-Me.sub.2 0 0 2463 CONMe.sub.2 SiMe.sub.3 H
2,6-Me.sub.2 0 0 2464 Ph H H 2-Me 0 0 2465 Ph H H 2-iPr 0 0 2466 Ph
H H 2-cPr 0 0 2467 Ph H H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2468 Ph
H H 2,6-Me.sub.2 0 0 2469 Ph H H 2-Me, 6-cPr 0 0 2470 Ph H H 3-CN 0
0 2471 Ph-3-CF.sub.3 H H 2-Me 0 0 2472 Ph-3-CN H H 2-iPr 0 0 2473
Ph-3-CN H H 2-cPr 0 0 2474 Ph-3-CN H H 2-CH.sub.2CH.sub.2CH.sub.2-3
0 0 2475 Ph-3-CN H H 2,6-Me.sub.2 0 0 2476 Ph-3-CN H H 2-Me, 6-cPr
0 0 2477 2-Fur H H 2-Me 0 0 2478 2-Thi H H 2-Me 0 0 2479 2-Thi H H
2-iPr 0 0 2480 2-Thi H H 2-cPr 0 0 2481 2-Thi H H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2482 2-Thi H H 2,6-Me.sub.2 0 0
2483 2-Thi H H 2-Me, 6-cPr 0 0 2484 OMe H H 2-Me 0 0 2485 O(Ph-2-F)
H H 2-F 0 0 2486 O(Ph-2-F) H H 2-Me 0 0 2487 O(Ph-2-F) H H 2-iPr 0
0 2488 O(Ph-2-F) H H 2-cPr 0 0 2489 O(Ph-2-F) H H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2490 O(Ph-2-F) H H 2,6-Me.sub.2 0
0 2491 O(Ph-2-F) H H 2-Me, 6-cPr 0 0 2492 O(Ph-2-Me) H H 2-Me 0 0
2493 O(Ph-2-Me) H H 2-iPr 0 0
2494 O(Ph-2-Me) H H 2-cPr 0 0 2495 O(Ph-2-Me) H H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2496 O(Ph-2-Me) H H 2,6-Me.sub.2 0
0 2497 O(Ph-2-Me) H H 2-Me, 6-cPr 0 0 2498 O(Ph-2-Me) CO.sub.2Et H
2-Me 0 0 2499 O(Ph-4-tBu) H H 4-tBu 0 0 2500 O(Ph-2-iPr-5-Me) H H
2-iPr, 5-Me 0 0 2501 O(Ph-2,3,5-Me.sub.3) H H 2,3,5-Me.sub.3 0 0
2502 O(Ph-2,4,6-Me.sub.3) H H 2,4,6-Me.sub.3 0 0 2503 O(Ph-2-cHx) H
H 2-cHx 0 0 2504 O(Ph-3-cN) H H 3-CN 0 0 2505 O(Ph-4-SiMe.sub.3) H
H 4-SiMe.sub.3 0 0 2506 OQ.sup.5 H H 2-Me 0 0 2507 OQ.sup.5 H H
2-iPr 0 0 2508 OQ.sup.5 H H 2-cPr 0 0 2509 OQ.sup.5 H H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2510 OQ.sup.5 H H 2,6-Me.sub.2 0 0
2511 OQ.sup.5 H H 2-Me, 6-cPr 0 0 2512 Cl H H 2-(cPr-1-F-2-F) 0 0
2513 Cl H H 2-(cPr-1-F-2-Cl) 0 0 2514 Cl H H 2-(cPr-1,2-Cl.sub.2) 0
0 2515 Cl H H 2-(cPr-1-Cl-2-Br) 0 0 2516 Cl H H
2-(cPr-1,2-Br.sub.2) 0 0 2517 Cl H H 2-(cPr-1-Me-2-Cl) 0 0 2518 Cl
H H 2-(cPr-1-Me-2-Br) 0 0 2519 Cl H H 2-(cPr-2-F-2-Cl) 0 0 2520 Cl
H H 2-(cPr-2-F-2-Br) 0 0 2521 Cl H H 2-(cPr-2-Cl-2-Br) 0 0 2522 Cl
H H 2-(cPr-1-Me-2,2-Cl.sub.2) 0 0 2523 Cl H H
2-(cPr-1-Me-2,2-Br.sub.2) 0 0 2524 Cl H H 2-(cPr-1-Me-2-F-2-Cl) 0 0
2525 Cl H H 2-C(F).dbd.CH.sub.2 0 0 2526 Cl H H
2-C(Cl).dbd.CH.sub.2 0 0 2527 Cl H H 2-C(Br).dbd.CH.sub.2 0 0 2528
Cl H H 2-C(Et).dbd.CH.sub.2 0 0 2529 Cl H H 2-C(iPr).dbd.CH.sub.2 0
0 2530 Cl H H 2-C(tBu).dbd.CH.sub.2 0 0 2531 Cl H H
2-C(CN).dbd.CH.sub.2 0 0 2532 Cl H H 2-CH.dbd.CHF 0 0 2533 Cl H H
2-CH.dbd.CHCl 0 0 2534 Cl H H 2-CH.dbd.CHBr 0 0 2535 Cl H H
2-CCl.dbd.CHC 0 0 2536 Cl H H 2-CMe.dbd.CHCl 0 0 2537 Cl H H
2-CH.dbd.CF.sub.2 0 0 2538 Cl H H 2-CH.dbd.CCl.sub.2 0 0 2539 Cl H
H 2-CH.dbd.CBr.sub.2 0 0 2540 Cl H H 2-CH.dbd.CMe.sub.2 0 0 2541 Cl
H H 2-CCl.dbd.CCl.sub.2 0 0 2542 Cl H H 2-CMe.dbd.CMe.sub.2 0 0
2543 Cl H H 2-CH.dbd.C(CN).sub.2 0 0 2544 Cl H H 3-OH 0 0 2545 Cl H
H 4-OH 0 0 2546 Cl H H 2-OCH.sub.2Ph 0 0 2547 Cl H H 3-OCH.sub.2Ph
0 0 2548 Cl H H 4-OCH.sub.2Ph 0 0 2549 Cl H H 2-I, 3-F 0 0 2550 Cl
H H 2-I, 3-Me 0 0 2551 Cl H H 2-I, 3-OMe 0 0 2552 Cl H H
2-CHMeCH.sub.2-3 0 0 2553 Cl H H 2-CMe.sub.2CH.sub.2-3 0 0 2554 Cl
H H 2-CH.sub.2CHMe-3 0 0 2555 Cl H H
2-CH.sub.2CH{(CH.sub.2).sub.3OH}-3 0 0 2556 Cl H H
2-CH.sub.2CMe.sub.2-3 0 0 2557 Cl H H 2-CH(CH.sub.2)CH-3 0 0 2558
Cl H H 2-CH(--CH.sub.2CH.sub.2--)CH.sub.2-3 0 0 2559 Cl H H
2-CHOMeCH.sub.2-3 0 0 2560 Cl H H 2-C(.dbd.O)CH.sub.2-3 0 0 2561 Cl
H H 2-CH.sub.2C(.dbd.O)-3 0 0 2562 Cl H H 2-C(.dbd.O)C(.dbd.O)-3 0
0 2563 Cl H H 2-CH.sub.2CH.sub.2NMe-3 0 0 2564 Cl H H
2-CH.dbd.CHNH-3 0 0 2565 Cl H H 2-CH.dbd.CHNMe-3 0 0 2566 Cl H H
2-NMeCH.sub.2CH.sub.2-3 0 0 2567 Cl H H 2-NHCH.dbd.CH-3 0 0 2568 Cl
H H 2-NMeCH.dbd.CH-3 0 0 2569 Cl H H 2-N(COMe)CH.dbd.CH-3 0 0 2570
Cl H H 2-Me, 4-COMe 0 0 2571 Cl H H 2-Me, 4-C(.dbd.NOMe)Me 0 0 2572
Cl H H 2-Me, 4-OCOMe 0 0 2573 Cl H H 2-Me, 4-OCOPh 0 0 2574 Cl H H
2-OMe, 5-CO.sub.2Me 0 0 2575 Cl H H 2-Me, 6-CH.sub.2F 0 0 2576 Cl H
H 2-Me, 6-CHF.sub.2 0 0 2577 Cl H H 2-Me, 6-CMe.dbd.CH.sub.2 0 0
2578 Cl H H 2-Me, 6-COMe 0 0 2579 Cl H H 2-Me, 6-C(.dbd.NOMe)Me 0 0
2580 Cl H H 2-OMe, 6-CO.sub.2Me 0 0 2581 Cl H H 2-Me, 6-OCOMe 0 0
2582 Cl H H 2-Me, 6-OCOPh 0 0 2583 Cl H H 3-Me, 4-F 0 0 2584 Cl H H
3-CH.sub.2CH.sub.2CH.sub.2-4 0 0 2585 Cl H H
3-CH.sub.2CH.sub.2CMe.sub.2-4 0 0 2586 Cl H H 2,6-Me.sub.2, 3-Br 0
0 2587 Cl H H 2-Me, 3-Br, 6-cPr 0 0 2588 Cl H H 2,6-Me.sub.2,
3-NO.sub.2 0 0 2589 Cl H H 2-Me, 3-NO.sub.2,6-cPr 0 0 2590 Cl H H
6-Cl, 2-CH.sub.2OCH.sub.2-3 0 0 2591 Cl H H 6-Br,
2-CH.sub.2OCH.sub.2-3 0 0 2592 Cl H H 6-Me, 2-CH.sub.2OCH.sub.2-3 0
0 2593 Cl H H 6-Et, 2-CH.sub.2OCH.sub.2-3 0 0 2594 Cl H H 6-iPr,
2-CH.sub.2OCH.sub.2-3 0 0 2595 Cl H H 6-cPr, 2-CH.sub.2OCH.sub.2-3
0 0 2596 Cl H H 2,4-Br.sub.2, 5-SEt 0 0 2597 Cl H H 2-F,
3,5,6-Me.sub.3 0 0 2598 Cl H H 2,3,5,6-Cl.sub.4 0 0 2599 Cl H H
2-Cl, 3,5,6-Me.sub.3 0 0 2600 Cl H H 2-I, 3,5,6-Me.sub.3 0 0 2601
Cl H H 2,3,3,6-Et 0 0 2602 Cl H H 2,3,5-Me.sub.3, 6-iPr 0 0 2603 Cl
H H 2,3,5-Me.sub.3, 6-CH.dbd.CH.sub.2 0 0 2604 Cl H H
2,3,5-Me.sub.3, 6-CCl.dbd.CH.sub.2 0 0 2605 Cl H H 2,3,5-Me.sub.3,
6-CMe.dbd.CH.sub.2 0 0 2606 Cl H H 2,3,5-Me.sub.3, 6-CH(SEt)Me 0 0
2607 Cl H H 2,3,5-Me.sub.3, 6-COMe 0 0 2608 Cl H H 2,3,5-Me.sub.3,
6-NO.sub.2 0 0 2609 Cl H H 2,4-Cl.sub.2, 3,5,6-Me.sub.3 0 0 2610 Cl
H H 2,3,4,5,6-F.sub.5 0 0 2611 Cl H H 2,3,4,5,6-Cl.sub.5 0 0 2612
Cl H H 2-Cl, 3,4,5,6-Me.sub.4 0 0 2613 Cl H H 2-Br,
3,4,5,6-Me.sub.4 0 0 2614 Cl H H 2,3,4,5,6-Me.sub.5 0 0 2615 Cl H H
2,3,4,4,6-Et 0 0 2616 Cl H H 2,3,4,5-Me.sub.4, 6-iPr 0 0 2617 Cl H
H 2,3,4,5-Me.sub.4, 6-cPr 0 0 2618 Cl H COEt 2-Cl 0 0 2619 Cl H
COEt 2-Br 0 0 2620 Cl H COEt 2-I 0 0 2621 Cl H COEt 2-cBu 0 0 2622
Cl H COEt 2-cPr, 5-Me 0 0 2623 Cl H COEt 2-OMe, 5-Me 0 0 2624 Cl H
COEt 2-F, 6-iPr 0 0 2625 Cl H COEt 2-Cl, 6-cPr 0 0 2626 Cl H COEt
2-Br, 6-Me 0 0 2627 Cl H COEt 2-I, 6-Me 0 0 2628 Cl H COEt 2-Me,
6-Et 0 0 2629 Cl H COEt 2,6-cPr.sub.2 0 0 2630 Cl H COEt 2-cPr,
3,5-Me.sub.2 0 0 2631 Cl H COEt 2-cPr, 3,6-Me.sub.2 0 0 2632 Cl H
COiPr 2-Cl 0 0 2633 Cl H COiPr 2-Br 0 0 2634 Cl H COiPr 2-I 0 0
2635 Cl H COiPr 2-cBu 0 0 2636 Cl H COiPr 2-cPr, 5-Me 0 0 2637 Cl H
COiPr 2-OMe, 5-Me 0 0 2638 Cl H COiPr 2-F, 6-iPr 0 0 2639 Cl H
COiPr 2-Cl, 6-cPr 0 0 2640 Cl H COiPr 2-Br, 6-Me 0 0 2641 Cl H
COiPr 2-I, 6-Me 0 0 2642 Cl H COiPr 2-Me, 6-Et 0 0 2643 Cl H COiPr
2,6-cPr.sub.2 0 0 2644 Cl H COiPr 2-cPr, 3,5-Me.sub.2 0 0 2645 Cl H
COiPr 2-cPr, 3,6-Me.sub.2 0 0 2646 Cl H COneoPen 2-Cl 0 0 2647 Cl H
COneoPen 2-Br 0 0 2648 Cl H COneoPen 2-I 0 0 2649 Cl H COneoPen
2-Me 0 0 2650 Cl H COneoPen 2-iPr 0 0 2651 Cl H COneoPen 2-cPr 0 0
2652 Cl H COneoPen 2-cBu 0 0 2653 Cl H COneoPen
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2654 Cl H COneoPen 2-cPr, 5-Me 0 0
2655 Cl H COneoPen 2-OMe, 5-Me 0 0 2656 Cl H COneoPen 2-F, 6-iPr 0
0 2657 Cl H COneoPen 2-Cl, 6-cPr 0 0 2658 Cl H COneoPen 2-Br, 6-Me
0 0 2659 Cl H COneoPen 2-I, 6-Me 0 0 2660 Cl H COneoPen
2,6-Me.sub.2 0 0 2661 Cl H COneoPen 2-Me, 6-Et 0 0 2662 Cl H
COneoPen 2-Me, 6-cPr 0 0 2663 Cl H COneoPen 2,6-cPr.sub.2 0 0 2664
Cl H COneoPen 2-cPr, 3,5-Me.sub.2 0 0 2665 Cl H COneoPen 2-cPr,
3,6-Me.sub.2 0 0 2666 Cl H CO(1-Ad) 2-Me 0 0 2667 Cl H CO(1-Ad)
2-iPr 0 0 2668 Cl H CO(1-Ad) 2-cPr 0 0 2669 Cl H CO(1-Ad)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2670 Cl H CO(1-Ad) 2,6-Me.sub.2 0
0 2671 Cl H CO(1-Ad) 2-Me, 6-cPr 0 0 2672 Cl H COCMe.dbd.CH.sub.2
2-Me 0 0 2673 Cl H COCMe.dbd.CH.sub.2 2-iPr 0 0 2674 Cl H
COCMe.dbd.CH.sub.2 2-cPr 0 0 2675 Cl H COCMe.dbd.CH.sub.2
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2676 Cl H COCMe.dbd.CH.sub.2
2,6-Me.sub.2 0 0 2677 Cl H COCMe.dbd.CH.sub.2 2-Me, 6-cPr 0 0 2678
Cl H COCH.dbd.CMe.sub.2 2-Cl 0 0 2679 Cl H COCH.dbd.CMe.sub.2 2-Br
0 0 2680 Cl H COCH.dbd.CMe.sub.2 2-I 0 0 2681 Cl H
COCH.dbd.CMe.sub.2 2-cBu 0 0 2682 Cl H COCH.dbd.CMe.sub.2 2-cPr,
5-Me 0 0 2683 Cl H COCH.dbd.CMe.sub.2 2-OMe, 5-Me 0 0 2684 Cl H
COCH.dbd.CMe.sub.2 2-F, 6-iPr 0 0 2685 Cl H COCH.dbd.CMe.sub.2
2-Cl, 6-cPr 0 0 2686 Cl H COCH.dbd.CMe.sub.2 2-Br, 6-Me 0 0 2687 Cl
H COCH.dbd.CMe.sub.2 2-I, 6-Me 0 0 2688 Cl H COCH.dbd.CMe.sub.2
2-Me, 6-Et 0 0 2689 Cl H COCH.dbd.CMe.sub.2 2,6-cPr.sub.2 0 0 2690
Cl H COCH.dbd.CMe.sub.2 2-cPr, 3,5-Me.sub.2 0 0 2691 Cl H
COCH.dbd.CMe.sub.2 2-cPr, 3,6-Me.sub.2 0 0 2692 Cl H COCMe.sub.2Br
2-Me 0 0 2693 Cl H COCMe.sub.2Br 2-iPr 0 0 2694 Cl H COCMe.sub.2Br
2-cPr 0 0 2695 Cl H COCMe.sub.2Br 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
2696 Cl H COCMe.sub.2Br 2,6-Me.sub.2 0 0 2697 Cl H COCMe.sub.2Br
2-Me, 6-cPr 0 0 2698 Cl H COCMe.sub.2CH.sub.2Cl 2-Me 0 0 2699 Cl H
COCMe.sub.2CH.sub.2Cl 2-iPr 0 0 2700 Cl H COCMe.sub.2CH.sub.2Cl
2-cPr 0 0 2701 Cl H COCMe.sub.2CH.sub.2Cl
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2702 Cl H COCMe.sub.2CH.sub.2Cl
2,6-Me.sub.2 0 0 2703 Cl H COCMe.sub.2CH.sub.2Cl 2-Me, 6-cPr 0 0
2704 Cl H COCH.sub.2CH.sub.2CH.sub.2CH.sub.2Br 2-Me 0 0 2705 Cl H
COCH.sub.2CH.sub.2CH.sub.2CH.sub.2Br 2-iPr 0 0 2706 Cl H
COCH.sub.2CH.sub.2CH.sub.2CH.sub.2Br 2-cPr 0 0 2707 Cl H
COCH.sub.2CH.sub.2CH.sub.2CH.sub.2Br 2-CH.sub.2CH.sub.2CH.sub.2-- 3
0 0 2708 Cl H COCH.sub.2CH.sub.2CH.sub.2CH.sub.2Br 2,6-Me.sub.2 0 0
2709 Cl H COCH.sub.2CH.sub.2CH.sub.2CH.sub.2Br 2-Me, 6-cPr 0 0 2710
Cl H COCHMePh 2-Me 0 0 2711 Cl H COCHMePh 2-iPr 0 0 2712 Cl H
COCHMePh 2-cPr 0 0 2713 Cl H COCHMePh 2-CH.sub.2CH.sub.2CH.sub.2-3
0 0 2714 Cl H COCHMePh 2,6-Me.sub.2 0 0 2715 Cl H COCHMePh 2-Me,
6-cPr 0 0 2716 Cl H COCH.sub.2 (Ph-4-OMe) 2-Me 0 0 2717 Cl H
COCH.sub.2 (Ph-4-OMe) 2-iPr 0 0 2718 Cl H COCH.sub.2 (Ph-4-OMe)
2-cPr 0 0 2719 Cl H COCH.sub.2 (Ph-4-OMe)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2720 Cl H COCH.sub.2 (Ph-4-OMe)
2,6-Me.sub.2 0 0 2721 Cl H COCH.sub.2 (Ph-4-OMe) 2-Me, 6-cPr 0 0
2722 Cl H COCH.sub.2CH.sub.2CO.sub.2Et 2-Me 0 0 2723 Cl H
COCH.sub.2CH.sub.2CO.sub.2Et 2-iPr 0 0 2724 Cl H
COCH.sub.2CH.sub.2CO.sub.2Et 2-cPr 0 0 2725 Cl H
COCH.sub.2CH.sub.2CO.sub.2Et 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2726
Cl H COCH.sub.2CH.sub.2CO.sub.2Et 2,6-Me.sub.2 0 0 2727 Cl H
COCH.sub.2CH.sub.2CO.sub.2Et 2-Me, 6-cPr 0 0 2728 Cl H
CO(CH.sub.2).sub.2CO.sub.2Q.sup.6 2-Me 0 0 2729 Cl H
CO(CH.sub.2).sub.2CO.sub.2Q.sup.7 2-iPr 0 0 2730 Cl H
CO(CH.sub.2).sub.2CO.sub.2Q.sup.8 2-cPr 0 0 2731 Cl H
CO(CH.sub.2).sub.2CO.sub.2Q.sup.9 2-CH.sub.2CH.sub.2CH.sub.2-3 0- 0
2732 Cl H CO(CH.sub.2).sub.2CO.sub.2Q.sup.10 2,6-Me.sub.2 0 0 2733
Cl H CO(CH.sub.2).sub.2CO.sub.2Q.sup.11 2-Me, 6-cPr 0 0 2734 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.5 2-Me 0 0 2735 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.5 2-iPr 0 0 2736 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.5 2-cPr 0 0 2737 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.5 2-CH.sub.2CH.sub.2CH.sub.2-3 0- 0
2738 Cl H CO(CH.sub.2).sub.3CO.sub.2Q.sup.5 2,6-Me.sub.2 0 0 2739
Cl H CO(CH.sub.2).sub.3CO.sub.2Q.sup.5 2-Me, 6-cPr 0 0 2740 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.12 2-Me, 6-cPr 0 0 2741 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.13 2-Me, 6-cPr 0 0
2742 Cl H CO(CH.sub.2).sub.3CO.sub.2Q.sup.14 2-Me, 6-cPr 0 0 2743
Cl H CO(CH.sub.2).sub.3CO.sub.2Q.sup.15 2-Me, 6-cPr 0 0 2744 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.16 2-Me, 6-cPr 0 0 2745 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.17 2-Me, 6-cPr 0 0 2746 Cl H
CO(CH.sub.2).sub.3CO.sub.2Q.sup.11 2-Me, 6-cPr 0 0 2747 Cl H
COCH.sub.2OMe 2-Me 0 0 2748 Cl H COCH.sub.2OMe 2-iPr 0 0 2749 Cl H
COCH.sub.2OMe 2-cPr 0 0 2750 Cl H COCH.sub.2OMe
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2751 Cl H COCH.sub.2OMe
2,6-Me.sub.2 0 0 2752 Cl H COCH.sub.2OMe 2-Me, 6-cPr 0 0 2753 Cl H
COCH.sub.2OPh 2-Me 0 0 2754 Cl H COCH.sub.2OPh 2-iPr 0 0 2755 Cl H
COCH.sub.2OPh 2-cPr 0 0 2756 Cl H COCH.sub.2OPh
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2757 Cl H COCH.sub.2OPh
2,6-Me.sub.2 0 0 2758 Cl H COCH.sub.2OPh 2-Me, 6-cPr 0 0 2759 Cl H
COCH(Me)OPh 2-Me 0 0 2760 Cl H COCH(Me)OPh 2-iPr 0 0 2761 Cl H
COCH(Me)OPh 2-cPr 0 0 2762 Cl H COCH(Me)OPh
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2763 Cl H COCH(Me)OPh 2,6-Me.sub.2
0 0 2764 Cl H COCH(Me)OPh 2-Me, 6-cPr 0 0 2765 Cl H COCH(OMe)Ph
2-Me 0 0 2766 Cl H COCH(OMe)Ph 2-iPr 0 0 2767 Cl H COCH(OMe)Ph
2-cPr 0 0 2768 Cl H COCH(OMe)Ph 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
2769 Cl H COCH(OMe)Ph 2,6-Me.sub.2 0 0 2770 Cl H COCH(OMe)Ph 2-Me,
6-cPr 0 0 2771 Cl H COCH.sub.2CH.sub.2SMe 2-Me 0 0 2772 Cl H
COCH.sub.2CH.sub.2SMe 2-iPr 0 0 2773 Cl H COCH.sub.2CH.sub.2SMe
2-cPr 0 0 2774 Cl H COCH.sub.2CH.sub.2SMe
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2775 Cl H COCH.sub.2CH.sub.2SMe
2,6-Me.sub.2 0 0 2776 Cl H COCH.sub.2CH.sub.2SMe 2-Me, 6-cPr 0 0
2777 Cl H COCO(2-Thi) 2-Me 0 0 2778 Cl H COCO(2-Thi) 2-iPr 0 0 2779
Cl H COCO(2-Thi) 2-cPr 0 0 2780 Cl H COCO(2-Thi)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2781 Cl H COCO(2-Thi) 2,6-Me.sub.2
0 0 2782 Cl H COCO(2-Thi) 2-Me, 6-cPr 0 0 2783 Cl H CO(Ph-2-F) 2-Me
0 0 2784 Cl H CO(Ph-2-F) 2-iPr 0 0 2785 Cl H CO(Ph-2-F) 2-cPr 0 0
2786 Cl H CO(Ph-2-F) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2787 Cl H
CO(Ph-2-F) 2,6-Me.sub.2 0 0 2788 Cl H CO(Ph-2-F) 2-Me, 6-cPr 0 0
2789 Cl H CO(Ph-2-Br) 2-Cl 0 0 2790 Cl H CO(Ph-2-Br) 2-Br 0 0 2791
Cl H CO(Ph-2-Br) 2-I 0 0 2792 Cl H CO(Ph-2-Br) 2-Me 0 0 2793 Cl H
CO(Ph-2-Br) 2-iPr 0 0 2794 Cl H CO(Ph-2-Br) 2-cPr 0 0 2795 Cl H
CO(Ph-2-Br) 2-cBu 0 0 2796 Cl H CO(Ph-2-Br)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2797 Cl H CO(Ph-2-Br) 2-cPr, 5-Me
0 0 2798 Cl H CO(Ph-2-Br) 2-OMe, 5-Me 0 0 2799 Cl H CO(Ph-2-Br)
2-F, 6-iPr 0 0 2800 Cl H CO(Ph-2-Br) 2-Cl, 6-cPr 0 0 2801 Cl H
CO(Ph-2-Br) 2-Br, 6-Me 0 0 2802 Cl H CO(Ph-2-Br) 2-I, 6-Me 0 0 2803
Cl H CO(Ph-2-Br) 2,6-Me.sub.2 0 0 2804 Cl H CO(Ph-2-Br) 2-Me, 6-Et
0 0 2805 Cl H CO(Ph-2-Br) 2-Me, 6-cPr 0 0 2806 Cl H CO(Ph-2-Br)
2,6-cPr.sub.2 0 0 2807 Cl H CO(Ph-2-Br) 2-cPr, 3,5-Me.sub.2 0 0
2808 Cl H CO(Ph-2-Br) 2-cPr, 3,6-Me.sub.2 0 0 2809 Cl H CO(Ph-2-I)
2-Me 0 0 2810 Cl H CO(Ph-2-I) 2-iPr 0 0 2811 Cl H CO(Ph-2-I) 2-cPr
0 0 2812 Cl H CO(Ph-2-I) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2813 Cl H
CO(Ph-2-I) 2,6-Me.sub.2 0 0 2814 Cl H CO(Ph-2-I) 2-Me, 6-cPr 0 0
2815 Cl H CO(Ph-2-CF.sub.3) 2-Me 0 0 2816 Cl H CO(Ph-2-CF.sub.3)
2-iPr 0 0 2817 Cl H CO(Ph-2-CF.sub.3) 2-cPr 0 0 2818 Cl H
CO(Ph-2-CF.sub.3) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2819 Cl H
CO(Ph-2-CF.sub.3) 2,6-Me.sub.2 0 0 2820 Cl H CO(Ph-2-CF.sub.3)
2-Me, 6-cPr 0 0 2821 Cl H CO(Ph-2-CH.sub.2Ph) 2-Me 0 0 2822 Cl H
CO(Ph-2-CH.sub.2Ph) 2-iPr 0 0 2823 Cl H CO(Ph-2-CH.sub.2Ph) 2-cPr 0
0 2824 Cl H CO(Ph-2-CH.sub.2Ph) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
2825 Cl H CO(Ph-2-CH.sub.2Ph) 2,6-Me.sub.2 0 0 2826 Cl H
CO(Ph-2-CH.sub.2Ph) 2-Me, 6-cPr 0 0 2827 Cl H
CO(Ph-2-CO.sub.2Q.sup.6) 2-Me 0 0 2828 Cl H
CO(Ph-2-CO.sub.2Q.sup.12) 2-Me 0 0 2829 Cl H
CO(Ph-2-CO.sub.2Q.sup.13) 2-Me 0 0 2830 Cl H
CO(Ph-2-CO.sub.2Q.sup.14) 2-Me 0 0 2831 Cl H
CO(Ph-2-CO.sub.2Q.sup.15) 2-Me 0 0 2832 Cl H
CO(Ph-2-CO.sub.2Q.sup.16) 2-Me 0 0 2833 Cl H
CO(Ph-2-CO.sub.2Q.sup.17) 2-Me 0 0 2834 Cl H
CO(Ph-2-CO.sub.2Q.sup.7) 2-iPr 0 0 2835 Cl H
CO(Ph-2-CO.sub.2Q.sup.8) 2-cPr 0 0 2836 Cl H
CO(Ph-2-CO.sub.2Q.sup.9) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2837 Cl H
CO(Ph-2-CO.sub.2Q.sup.10) 2,6-Me.sub.2 0 0 2838 Cl H
CO(Ph-2-CO.sub.2Q.sup.11) 2-Me, 6-cPr 0 0 2839 Cl H
CO(Ph-2-CO.sub.2Q.sup.12) 2-Me, 6-cPr 0 0 2840 Cl H
CO(Ph-2-CO.sub.2Q.sup.13) 2-Me, 6-cPr 0 0 2841 Cl H
CO(Ph-2-CO.sub.2Q.sup.14) 2-Me, 6-cPr 0 0 2842 Cl H
CO(Ph-2-CO.sub.2Q.sup.15) 2-Me, 6-cPr 0 0 2843 Cl H
CO(Ph-2-CO.sub.2Q.sup.16) 2-Me, 6-cPr 0 0 2844 Cl H
CO(Ph-2-CO.sub.2Q.sup.17) 2-Me, 6-cPr 0 0 2845 Cl H
CO(Ph-2-NO.sub.2) 2-Me 0 0 2846 Cl H CO(Ph-2-NO.sub.2) 2-iPr 0 0
2847 Cl H CO(Ph-2-NO.sub.2) 2-cPr 0 0 2848 Cl H CO(Ph-2-NO.sub.2)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2849 Cl H CO(Ph-2-NO.sub.2)
2,6-Me.sub.2 0 0 2850 Cl H CO(Ph-2-NO.sub.2) 2-Me, 6-cPr 0 0 2851
Cl H CO(Ph-2-OPh) 2-Me 0 0 2852 Cl H CO(Ph-2-OPh) 2-iPr 0 0 2853 Cl
H CO(Ph-2-OPh) 2-cPr 0 0 2854 Cl H CO(Ph-2-OPh)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2855 Cl H CO(Ph-2-OPh)
2,6-Me.sub.2 0 0 2856 Cl H CO(Ph-2-OPh) 2-Me, 6-cPr 0 0 2857 Cl H
CO(Ph-3-F) 2-Me 0 0 2858 Cl H CO(Ph-3-F) 2-iPr 0 0 2859 Cl H
CO(Ph-3-F) 2-cPr 0 0 2860 Cl H CO(Ph-3-F)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2861 Cl H CO(Ph-3-F) 2,6-Me.sub.2
0 0 2862 Cl H CO(Ph-3-F) 2-Me, 6-cPr 0 0 2863 Cl H CO(Ph-3-Cl) 2-Me
0 0 2864 Cl H CO(Ph-3-Cl) 2-iPr 0 0 2865 Cl H CO(Ph-3-Cl) 2-cPr 0 0
2866 Cl H CO(Ph-3-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2867 Cl H
CO(Ph-3-Cl) 2,6-Me.sub.2 0 0 2868 Cl H CO(Ph-3-Cl) 2-Me, 6-cPr 0 0
2869 Cl H CO(Ph-3-Br) 2-Me 0 0 2870 Cl H CO(Ph-3-Br) 2-iPr 0 0 2871
Cl H CO(Ph-3-Br) 2-cPr 0 0 2872 Cl H CO(Ph-3-Br)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2873 Cl H CO(Ph-3-Br) 2,6-Me.sub.2
0 0 2874 Cl H CO(Ph-3-Br) 2-Me, 6-cPr 0 0 2875 Cl H CO(Ph-3-I) 2-Me
0 0 2876 Cl H CO(Ph-3-I) 2-iPr 0 0 2877 Cl H CO(Ph-3-I) 2-cPr 0 0
2878 Cl H CO(Ph-3-I) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2879 Cl H
CO(Ph-3-I) 2,6-Me.sub.2 0 0 2880 Cl H CO(Ph-3-I) 2-Me, 6-cPr 0 0
2881 Cl H CO(Ph-3-Me) 2-Cl 0 0 2882 Cl H CO(Ph-3-Me) 2-Br 0 0 2883
Cl H CO(Ph-3-Me) 2-I 0 0 2884 Cl H CO(Ph-3-Me) 2-cBu 0 0 2885 Cl H
CO(Ph-3--Me) 2-cPr, 5-Me 0 0 2886 Cl H CO(Ph-3-Me) 2-OMe, 5-Me 0 0
2887 Cl H CO(Ph-3-Me) 2-F, 6-iPr 0 0 2888 Cl H CO(Ph-3-Me) 2-Cl,
6-cPr 0 0 2889 Cl H CO(Ph-3-Me) 2-Br, 6-Me 0 0 2890 Cl H
CO(Ph-3-Me) 2-I, 6-Me 0 0 2891 Cl H CO(Ph-3-Me) 2-Me, 6-Et 0 0 2892
Cl H CO(Ph-3-Me) 2,6-cPr.sub.2 0 0 2893 Cl H CO(Ph-3-Me) 2-cPr,
3,5-Me.sub.2 0 0 2894 Cl H CO(Ph-3-Me) 2-cPr, 3,6-Me.sub.2 0 0 2895
Cl H CO(Ph-3-CF.sub.3) 2-Me 0 0 2896 Cl H CO(Ph-3-CF.sub.3) 2-iPr 0
0 2897 Cl H CO(Ph-3-CF.sub.3) 2-cPr 0 0 2898 Cl H CO(Ph-3-CF.sub.3)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2899 Cl H CO(Ph-3-CF.sub.3)
2,6-Me.sub.2 0 0 2900 Cl H CO(Ph-3-CF.sub.3) 2-Me, 6-cPr 0 0 2901
Cl H CO(Ph-3-CO.sub.2Q.sup.6) 2-Me 0 0 2902 Cl H
CO(Ph-3-CO.sub.2Q.sup.7) 2-iPr 0 0 2903 Cl H
CO(Ph-3-CO.sub.2Q.sup.8) 2-cPr 0 0 2904 Cl H
CO(Ph-3-CO.sub.2Q.sup.9) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2905 Cl H
CO(Ph-3-CO.sub.2Q.sup.10) 2,6-Me.sub.2 0 0 2906 Cl H
CO(Ph-3-CO.sub.2Q.sup.11) 2-Me, 6-cPr 0 0 2907 Cl H
CO(Ph-3-CO.sub.2Q.sup.12) 2-Me, 6-cPr 0 0 2908 Cl H
CO(Ph-3-CO.sub.2Q.sup.13) 2-Me, 6-cPr 0 0 2909 Cl H
CO(Ph-3-CO.sub.2Q.sup.14) 2-Me, 6-cPr 0 0 2910 Cl H
CO(Ph-3-CO.sub.2Q.sup.15) 2-Me, 6-cPr 0 0 2911 Cl H
CO(Ph-3-CO.sub.2Q.sup.16) 2-Me, 6-cPr 0 0 2912 Cl H
CO(Ph-3-CO.sub.2Q.sup.17) 2-Me., 6-cPr 0 0 2913 Cl H
CO(Ph-3-NO.sub.2) 2-Me 0 0 2914 Cl H CO(Ph-3-NO.sub.2) 2-iPr 0 0
2915 Cl H CO(Ph-3-NO.sub.2) 2-cPr 0 0 2916 Cl H CO(Ph-3-NO.sub.2)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2917 Cl H CO(Ph-3-NO.sub.2)
2,6-Me.sub.2 0 0 2918 Cl H CO(Ph-3-NO.sub.2) 2-Me, 6-cPr 0 0 2919
Cl H CO(Ph-3-OPh) 2-Me 0 0 2920 Cl H CO(Ph-3-OPh) 2-iPr 0 0 2921 Cl
H CO(Ph-3-OPh) 2-cPr 0 0 2922 Cl H CO(Ph-3-OPh)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2923 Cl H CO(Ph-3-OPh)
2,6-Me.sub.2 0 0 2924 Cl H CO(Ph-3-OPh) 2-Me, 6-cPr 0 0 2925 Cl H
CO(Ph-4-F) 2-Me 0 0 2926 Cl H CO(Ph-4-F) 2-iPr 0 0 2927 Cl H
CO(Ph-4-F) 2-cPr 0 0 2928 Cl H CO(Ph-4-F)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2929 Cl H CO(Ph-4-F) 2,6-Me.sub.2
0 0 2930 Cl H CO(Ph-4-F) 2-Me, 6-cPr 0 0 2931 Cl H CO(Ph-4-Br) 2-Cl
0 0 2932 Cl H CO(Ph-4-Br) 2-Br 0 0 2933 Cl H CO(Ph-4-Br) 2-I 0 0
2934 Cl H CO(Ph-4-Br) 2-cBu 0 0 2935 Cl H CO(Ph-4-Br) 2-cPr, 5-Me 0
0 2936 Cl H CO(Ph-4-Br) 2-OMe, 5-Me 0 0 2937 Cl H CO(Ph-4-Br) 2-F,
6-iPr 0 0 2938 Cl H CO(Ph-4-Br) 2-Cl, 6-cPr 0 0 2939 Cl H
CO(Ph-4-Br) 2-Br, 6-Me 0 0 2940 Cl H CO(Ph-4-Br) 2-I, 6-Me 0 0 2941
Cl H CO(Ph-4-Br) 2-Me, 6-Et 0 0 2942 Cl H CO(Ph-4-Br) 2,6-cPr.sub.2
0 0 2943 Cl H CO(Ph-4-Br) 2-cPr, 3,5-Me.sub.2 0 0 2944 Cl H
CO(Ph-4-Br) 2-cPr, 3,6-Me.sub.2 0 0 2945 Cl H CO(Ph-4-Et) 2-Cl 0 0
2946 Cl H CO(Ph-4-Et) 2-Br 0 0 2947 Cl H CO(Ph-4-Et) 2-I 0 0 2948
Cl H CO(Ph-4-Et) 2-Me 0 0 2949 Cl H CO(Ph-4-Et) 2-iPr 0 0 2950 Cl H
CO(Ph-4-Et) 2-cPr 0 0 2951 Cl H CO(Ph-4-Et) 2-cBu 0 0 2952 Cl H
CO(Ph-4-Et) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2953 Cl H CO(Ph-4-Et)
2-cPr, 5-Me 0 0 2954 Cl H CO(Ph-4-Et) 2-OMe, 5-Me 0 0 2955 Cl H
CO(Ph-4-Et) 2-F, 6-iPr 0 0 2956 Cl H CO(Ph-4-Et) 2-Cl, 6-cPr 0 0
2957 Cl H CO(Ph-4-Et) 2-Br, 6-Me 0 0 2958 Cl H CO(Ph-4-Et) 2-I,
6-Me 0 0 2959 Cl H CO(Ph-4-Et) 2,6-Me.sub.2 0 0 2960 Cl H
CO(Ph-4-Et) 2-Me, 6-Et 0 0 2961 Cl H CO(Ph-4-Et) 2-Me, 6-cPr 0 0
2962 Cl H CO(Ph-4-Et) 2,6-cPr.sub.2 0 0 2963 Cl H CO(Ph-4-Et)
2-cPr, 3,5-Me.sub.2 0 0 2964 Cl H CO(Ph-4-Et) 2-cPr, 3,6-Me.sub.2 0
0 2965 Cl H CO(Ph-4-Pr) 2-Me 0 0 2966 Cl H CO(Ph-4-Pr) 2-iPr 0 0
2967 Cl H CO(Ph-4-Pr) 2-cPr 0 0 2968 Cl H CO(Ph-4-Pr)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2969 Cl H CO(Ph-4-Pr) 2,6-Me.sub.2
0 0 2970 Cl H CO(Ph-4-Pr) 2-Me, 6-cPr 0 0 2971 Cl H CO(Ph-4-iPr)
2-Me 0 0 2972 Cl H CO(Ph-4-iPr) 2-iPr 0 0 2973 Cl H CO(Ph-4-iPr)
2-cPr 0 0 2974 Cl H CO(Ph-4-iPr) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
2975 Cl H CO(Ph-4-iPr) 2,6-Me.sub.2 0 0 2976 Cl H CO(Ph-4-iPr)
2-Me, 6-cPr 0 0 2977 Cl H CO(Ph-4-Bu) 2-Me 0 0 2978 Cl H
CO(Ph-4-Bu) 2-iPr 0 0 2979 Cl H CO(Ph-4-Bu) 2-cPr 0 0 2980 Cl H
CO(Ph-4-Bu) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2981 Cl H CO(Ph-4-Bu)
2,6-Me.sub.2 0 0 2982 Cl H CO(Ph-4-Bu) 2-Me, 6-cPr 0 0 2983 Cl H
CO(Ph-4-CF.sub.3) 2-Me 0 0 2984 Cl H CO(Ph-4-CF.sub.3) 2-iPr 0 0
2985 Cl H CO(Ph-4-CF.sub.3) 2-cPr 0 0 2986 Cl H CO(Ph-4-CF.sub.3)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 2987 Cl H CO(Ph-4-CF.sub.3)
2,6-Me.sub.2 0 0 2988 Cl H CO(Ph-4-CF.sub.3) 2-Me, 6-cPr 0 0 2989
Cl H CO(Ph-4-CN) 2-Me 0 0 2990 Cl H CO(Ph-4-CN) 2-iPr 0 0 2991 Cl H
CO(Ph-4-CN) 2-cPr 0 0 2992 Cl H CO(Ph-4-CN)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
2993 Cl H CO(Ph-4-CN) 2,6-Me.sub.2 0 0 2994 Cl H CO(Ph-4-CN) 2-Me,
6-cPr 0 0 2995 Cl H CO(Ph-4-CO.sub.2Q.sup.5) 2-Cl, 6-cPr 0 0 2996
Cl H CO(Ph-4-CO.sub.2Q.sup.6) 2-Me 0 0 2997 Cl H
CO(Ph-4-CO.sub.2Q.sup.7) 2-iPr 0 0 2998 Cl H
CO(Ph-4-CO.sub.2Q.sup.8) 2-cPr 0 0 2999 Cl H
CO(Ph-4-CO.sub.2Q.sup.9) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3000 Cl H
CO(Ph-4-CO.sub.2Q.sup.10) 2,6-Me.sub.2 0 0 3001 Cl H
CO(Ph-4-CO.sub.2Q.sup.11) 2-Me, 6-cPr 0 0 3002 Cl H
CO(Ph-4-CO.sub.2Q.sup.12) 2-Me, 6-cPr 0 0 3003 Cl H
CO(Ph-4-CO.sub.2Q.sup.13) 2-Me, 6-cPr 0 0 3004 Cl H
CO(Ph-4-CO.sub.2Q.sup.14) 2-Me, 6-cPr 0 0 3005 Cl H
CO(Ph-4-CO.sub.2Q.sup.15) 2-Me, 6-cPr 0 0 3006 Cl H
CO(Ph-4-CO.sub.2Q.sup.16) 2-Me, 6-cPr 0 0 3007 Cl H
CO(Ph-4-CO.sub.2Q.sup.17) 2-Me, 6-cPr 0 0 3008 Cl H
CO(Ph-2-SO.sub.2OQ.sup.5) 2-Me, 6-cPr 0 0 3009 Cl H
CO(Ph-3-SO.sub.2OQ.sup.5) 2-Me, 6-cPr 0 0 3010 Cl H
CO(Ph-4-SO.sub.2OQ.sup.5) 2-Me, 6-cPr 0 0 3011 Cl H CO(Ph-4-Ph)
2-Me 0 0 3012 Cl H CO(Ph-4-Ph) 2-iPr 0 0 3013 Cl H CO(Ph-4-Ph)
2-cPr 0 0 3014 Cl H CO(Ph-4-Ph) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3015 Cl H CO(Ph-4-Ph) 2,6-Me.sub.2 0 0 3016 Cl H CO(Ph-4-Ph) 2-Me,
6-cPr 0 0 3017 Cl H CO(Ph-4-OCF.sub.3) 2-Me 0 0 3018 Cl H
CO(Ph-4-OCF.sub.3) 2-iPr 0 0 3019 Cl H CO(Ph-4-OCF.sub.3) 2-cPr 0 0
3020 Cl H CO(Ph-4-OCF.sub.3) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3021
Cl H CO(Ph-4-OCF.sub.3) 2,6-Me.sub.2 0 0 3022 Cl H
CO(Ph-4-OCF.sub.3) 2-Me, 6-cPr 0 0 3023 Cl H CO(Ph-4-OCH.sub.2Ph)
2-Me 0 0 3024 Cl H CO(Ph-4-OCH.sub.2Ph) 2-iPr 0 0 3025 Cl H
CO(Ph-4-OCH.sub.2Ph) 2-cPr 0 0 3026 Cl H CO(Ph-4-OCH.sub.2Ph)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3027 Cl H CO(Ph-4-OCH.sub.2Ph)
2,6-Me.sub.2 0 0 3028 Cl H CO(Ph-4-OCH.sub.2Ph) 2-Me, 6-cPr 0 0
3029 Cl H CO(Ph-2,3-F.sub.2) 2-Me 0 0 3030 Cl H CO(Ph-2,3-F.sub.2)
2-iPr 0 0 3031 Cl H CO(Ph-2,3-F.sub.2) 2-cPr 0 0 3032 Cl H
CO(Ph-2,3-F.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3033 Cl H
CO(Ph-2,3-F.sub.2) 2,6-Me.sub.2 0 0 3034 Cl H CO(Ph-2,3-F.sub.2)
2-Me, 6-cPr 0 0 3035 Cl H CO(Ph-2-F-3-CF.sub.3) 2-Me 0 0 3036 Cl H
CO(Ph-2-F-3-CF.sub.3) 2-iPr 0 0 3037 Cl H CO(Ph-2-F-3-CF.sub.3)
2-cPr 0 0 3038 Cl H CO(Ph-2-F-3-CF.sub.3)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3039 Cl H CO(Ph-2-F-3-CF.sub.3)
2,6-Me.sub.2 0 0 3040 Cl H CO(Ph-2-F-3-CF.sub.3) 2-Me, 6-cPr 0 0
3041 Cl H CO(Ph-2,3-Me.sub.2) 2-Me 0 0 3042 Cl H
CO(Ph-2,3-Me.sub.2) 2-iPr 0 0 3043 Cl H CO(Ph-2,3-Me.sub.2) 2-cPr 0
0 3044 Cl H CO(Ph-2,3-Me.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3045 Cl H CO(Ph-2,3-Me.sub.2) 2,6-Me.sub.2 0 0 3046 Cl H
CO(Ph-2,3-Me.sub.2) 2-Me, 6-cPr 0 0 3047 Cl H CO(Ph-2-Me-3-Cl) 2-Me
0 0 3048 Cl H CO(Ph-2-Me-3-Cl) 2-iPr 0 0 3049 Cl H CO(Ph-2-Me-3-Cl)
2-cPr 0 0 3050 Cl H CO(Ph-2-Me-3-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0
0 3051 Cl H CO(Ph-2-Me-3-Cl) 2,6-Me.sub.2 0 0 3052 Cl H
CO(Ph-2-Me-3-Cl) 2-Me, 6-cPr 0 0 3053 Cl H CO(Ph-2,4-F.sub.2) 2-Me
0 0 3054 Cl H CO(Ph-2,4-F.sub.2) 2-iPr 0 0 3055 Cl H
CO(Ph-2,4-F.sub.2) 2-cPr 0 0 3056 Cl H CO(Ph-2,4-F.sub.2)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3057 Cl H CO(Ph-2,4-F.sub.2)
2,6-Me.sub.2 0 0 3058 Cl H CO(Ph-2,4-F.sub.2) 2-Me, 6-cPr 0 0 3059
Cl H CO(Ph-2-F-4-Cl) 2-Me 0 0 3060 Cl H CO(Ph-2-F-4-Cl) 2-iPr 0 0
3061 Cl H CO(Ph-2-F-4-Cl) 2-cPr 0 0 3062 Cl H CO(Ph-2-F-4-Cl)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3063 Cl H CO(Ph-2-F-4-Cl)
2,6-Me.sub.2 0 0 3064 Cl H CO(Ph-2-F-4-Cl) 2-Me, 6-cPr 0 0 3065 Cl
H CO(Ph-2-F-4-CF.sub.3) 2-Me 0 0 3066 Cl H CO(Ph-2-F-4-CF.sub.3)
2-iPr 0 0 3067 Cl H CO(Ph-2-F-4-CF.sub.3) 2-cPr 0 0 3068 Cl H
CO(Ph-2-F-4-CF.sub.3) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3069 Cl H
CO(Ph-2-F-4-CF.sub.3) 2,6-Me.sub.2 0 0 3070 Cl H
CO(Ph-2-F-4-CF.sub.3) 2-Me, 6-cPr 0 0 3071 Cl H CO(Ph-2-Cl-4-F)
2-Me 0 0 3072 Cl H CO(Ph-2-Cl-4-F) 2-iPr 0 0 3073 Cl H
CO(Ph-2-Cl-4-F) 2-cPr 0 0 3074 Cl H CO(Ph-2-Cl-4-F)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3075 Cl H CO(Ph-2-Cl-4-F)
2,6-Me.sub.2 0 0 3076 Cl H CO(Ph-2-Cl-4-F) 2-Me, 6-cPr 0 0 3077 Cl
H CO(Ph-2-Cl-4-Br) 2-Me 0 0 3078 Cl H CO(Ph-2-Cl-4-Br) 2-iPr 0 0
3079 Cl H CO(Ph-2-Cl-4-Br) 2-cPr 0 0 3080 Cl H CO(Ph-2-Cl-4-Br)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3081 Cl H CO(Ph-2-Cl-4-Br)
2,6-Me.sub.2 0 0 3082 Cl H CO(Ph-2-Cl-4-Br) 2-Me, 6-cPr 0 0 3083 Cl
H CO(Ph-2-Me-4-Br) 2-Me 0 0 3084 Cl H CO(Ph-2-Me-4-Br) 2-iPr 0 0
3085 Cl H CO(Ph-2-Me-4-Br) 2-cPr 0 0 3086 Cl H CO(Ph-2-Me-4-Br)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3087 Cl H CO(Ph-2-Me-4-Br)
2,6-Me.sub.2 0 0 3088 Cl H CO(Ph-2-Me-4-Br) 2-Me, 6-cPr 0 0 3089 Cl
H CO(Ph-2,4-Me.sub.2) 2-Me 0 0 3090 Cl H CO(Ph-2,4-Me.sub.2) 2-iPr
0 0 3091 Cl H CO(Ph-2,4-Me.sub.2) 2-cPr 0 0 3092 Cl H
CO(Ph-2,4-Me.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3093 Cl H
CO(Ph-2,4-Me.sub.2) 2,6-Me.sub.2 0 0 3094 Cl H CO(Ph-2,4-Me.sub.2)
2-Me, 6-cPr 0 0 3095 Cl H CO(Ph-2,5-Cl.sub.2) 2-Me 0 0 3096 Cl H
CO(Ph-2,5-Cl.sub.2) 2-iPr 0 0 3097 Cl H CO(Ph-2,5-Cl.sub.2) 2-cPr 0
0 3098 Cl H CO(Ph-2,5-Cl.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3099 Cl H CO(Ph-2,5-Cl.sub.2) 2,6-Me.sub.2 0 0 3100 Cl H
CO(Ph-2,5-Cl.sub.2) 2-Me, 6-cPr 0 0 3101 Cl H CO(Ph-2-Cl-5-Br) 2-Me
0 0 3102 Cl H CO(Ph-2-Cl-5-Br) 2-iPr 0 0 3103 Cl H CO(Ph-2-Cl-5-Br)
2-cPr 0 0 3104 Cl H CO(Ph-2-Cl-5-Br) 2-CH.sub.2CH.sub.2CH.sub.2-3 0
0 3105 Cl H CO(Ph-2-Cl-5-Br) 2,6-Me.sub.2 0 0 3106 Cl H
CO(Ph-2-Cl-5-Br) 2-Me, 6-cPr 0 0 3107 Cl H CO(Ph-2-Br-5-OMe) 2-Me 0
0 3108 Cl H CO(Ph-2-Br-5-OMe) 2-iPr 0 0 3109 Cl H CO(Ph-2-Br-5-OMe)
2-cPr 0 0 3110 Cl H CO(Ph-2-Br-5-OMe) 2-CH.sub.2CH.sub.2CH.sub.2-3
0 0 3111 Cl H CO(Ph-2-Br-5-OMe) 2,6-Me.sub.2 0 0 3112 Cl H
CO(Ph-2-Br-5-OMe) 2-Me, 6-cPr 0 0 3113 Cl H CO(Ph-2,5-Me.sub.2)
2-Cl 0 0 3114 Cl H CO(Ph-2,5-Me.sub.2) 2-Br 0 0 3115 Cl H
CO(Ph-2,5-Me.sub.2) 2-I 0 0 3116 Cl H CO(Ph-2,5-Me.sub.2) 2-Me 0 0
3117 Cl H CO(Ph-2,5-Me.sub.2) 2-iPr 0 0 3118 Cl H
CO(Ph-2,5-Me.sub.2) 2-cPr 0 0 3119 Cl H CO(Ph-2,5-Me.sub.2) 2-cBu 0
0 3120 Cl H CO(Ph-2,5-Me.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3121 Cl H CO(Ph-2,5-Me.sub.2) 2-cPr, 5-Me 0 0 3122 Cl H
CO(Ph-2,5-Me.sub.2) 2-OMe, 5-Me 0 0 3123 Cl H CO(Ph-2,5-Me.sub.2)
2-F, 6-iPr 0 0 3124 Cl H CO(Ph-2,5-Me.sub.2) 2-Cl, 6-cPr 0 0 3125
Cl H CO(Ph-2,5-Me.sub.2) 2-Br, 6-Me 0 0 3126 Cl H
CO(Ph-2,5-Me.sub.2) 2-I, 6-Me 0 0 3127 Cl H CO(Ph-2,5-Me.sub.2)
2,6-Me.sub.2 0 0 3128 Cl H CO(Ph-2,5-Me.sub.2) 2-Me, 6-Et 0 0 3129
Cl H CO(Ph-2,5-Me.sub.2) 2-Me, 6-cPr 0 0 3130 Cl H
CO(Ph-2,5-Me.sub.2) 2,6-cPr.sub.2 0 0 3131 Cl H CO(Ph-2,5-Me.sub.2)
2-cPr, 3,5-Me.sub.2 0 0 3132 Cl H CO(Ph-2,5-Me.sub.2) 2-cPr,
3,6-Me.sub.2 0 0 3133 Cl H CO(Ph-2,6-F.sub.2) 2-Me 0 0 3134 Cl H
CO(Ph-2,6-F.sub.2) 2-iPr 0 0 3135 Cl H CO(Ph-2,6-F.sub.2) 2-cPr 0 0
3136 Cl H CO(Ph-2,6-F.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3137
Cl H CO(Ph-2,6-F.sub.2) 2,6-Me.sub.2 0 0 3138 Cl H
CO(Ph-2,6-F.sub.2) 2-Me, 6-cPr 0 0 3139 Cl H CO(Ph-2-F-6-Cl) 2-Me 0
0 3140 Cl H CO(Ph-2-F-6-Cl) 2-iPr 0 0 3141 Cl H CO(Ph-2-F-6-Cl)
2-cPr 0 0 3142 Cl H CO(Ph-2-F-6-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0
0 3143 Cl H CO(Ph-2-F-6-Cl) 2,6-Me.sub.2 0 0 3144 Cl H
CO(Ph-2-F-6-Cl) 2-Me, 6-cPr 0 0 3145 Cl H CO(Ph-2,6-Cl.sub.2) 2-Me
0 0 3146 Cl H CO(Ph-2,6-Cl.sub.2) 2-iPr 0 0 3147 Cl H
CO(Ph-2,6-Cl.sub.2) 2-cPr 0 0 3148 Cl H CO(Ph-2,6-Cl.sub.2)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3149 Cl H CO(Ph-2,6-Cl.sub.2)
2,6-Me.sub.2 0 0 3150 Cl H CO(Ph-2,6-Cl.sub.2) 2-Me, 6-cPr 0 0 3151
Cl H CO(Ph-2,6-Me.sub.2) 2-Me 0 0 3152 Cl H CO(Ph-2,6-Me.sub.2)
2-iPr 0 0 3153 Cl H CO(Ph-2,6-Me.sub.2) 2-cPr 0 0 3154 Cl H
CO(Ph-2,6-Me.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3155 Cl H
CO(Ph-2,6-Me.sub.2) 2,6-Me.sub.2 0 0 3156 Cl H CO(Ph-2,6-Me.sub.2)
2-Me, 6-cPr 0 0 3157 Cl H CO{Ph-2,6-(OMe).sub.2} 2-Me 0 0 3158 Cl H
CO{Ph-2,6-(OMe).sub.2} 2-iPr 0 0 3159 Cl H CO{Ph-2,6-(OMe).sub.2}
2-cPr 0 0 3160 Cl H CO{Ph-2,6-(OMe).sub.2}
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3161 Cl H CO{Ph-2,6-(OMe).sub.2}
2,6-Me.sub.2 0 0 3162 Cl H CO{Ph-2,6-(OMe).sub.2} 2-Me, 6-cPr 0 0
3163 Cl H CO(Ph-3,4-F.sub.2) 2-Me 0 0 3164 Cl H CO(Ph-3,4-F.sub.2)
2-iPr 0 0 3165 Cl H CO(Ph-3,4-F.sub.2) 2-cPr 0 0 3166 Cl H
CO(Ph-3,4-F.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3167 Cl H
CO(Ph-3,4-F.sub.2) 2,6-Me.sub.2 0 0 3168 Cl H CO(Ph-3,4-F.sub.2)
2-Me, 6-cPr 0 0 3169 Cl H CO(Ph-3-F-4-Me) 2-Cl 0 0 3170 Cl H
CO(Ph-3-F-4-Me) 2-Br 0 0 3171 Cl H CO(Ph-3-F-4-Me) 2-I 0 0 3172 Cl
H CO(Ph-3-F-4-Me) 2-Me 0 0 3173 Cl H CO(Ph-3-F-4-Me) 2-iPr 0 0 3174
Cl H CO(Ph-3-F-4-Me) 2-cPr 0 0 3175 Cl H CO(Ph-3-F-4-Me) 2-cBu 0 0
3176 Cl H CO(Ph-3-F-4-Me) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3177 Cl
H CO(Ph-3-F-4-Me) 2-cPr, 5-Me 0 0 3178 Cl H CO(Ph-3-F-4-Me) 2-OMe,
5-Me 0 0 3179 Cl H CO(Ph-3-F-4-Me) 2-F, 6-iPr 0 0 3180 Cl H
CO(Ph-3-F-4-Me) 2-Cl, 6-cPr 0 0 3181 Cl H CO(Ph-3-F-4-Me) 2-Br,
6-Me 0 0 3182 Cl H CO(Ph-3-F-4-Me) 2-I, 6-Me 0 0 3183 Cl H
CO(Ph-3-F-4-Me) 2,6-Me.sub.2 0 0 3184 Cl H CO(Ph-3-F-4-Me) 2-Me,
6-Et 0 0 3185 Cl H CO(Ph-3-F-4-Me) 2-Me, 6-cPr 0 0 3186 Cl H
CO(Ph-3-F-4-Me) 2,6-cPr.sub.2 0 0 3187 Cl H CO(Ph-3-F-4-Me) 2-cPr,
3,5-Me.sub.2 0 0 3188 Cl H CO(Ph-3-F-4-Me) 2-cPr, 3,6-Me.sub.2 0 0
3189 Cl H CO(Ph-3,4-Cl.sub.2) 2-Me 0 0 3190 Cl H
CO(Ph-3,4-Cl.sub.2) 2-iPr 0 0 3191 Cl H CO(Ph-3,4-Cl.sub.2) 2-cPr 0
0 3192 Cl H CO(Ph-3,4-Cl.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3193 Cl H CO(Ph-3,4-Cl.sub.2) 2,6-Me.sub.2 0 0 3194 Cl H
CO(Ph-3,4-Cl.sub.2) 2-Me, 6-cPr 0 0 3195 Cl H
CO(Ph-3-NO.sub.2-4-Cl) 2-Me 0 0 3196 Cl H CO(Ph-3-NO.sub.2-4-Cl)
2-iPr 0 0 3197 Cl H CO(Ph-3-NO.sub.2-4-Cl) 2-cPr 0 0 3198 Cl H
CO(Ph-3-NO.sub.2-4-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3199 Cl H
CO(Ph-3-NO.sub.2-4-Cl) 2,6-Me.sub.2 0 0 3200 Cl H
CO(Ph-3-NO.sub.2-4-Cl) 2-Me, 6-cPr 0 0 3201 Cl H CO(Ph-3,5-F.sub.2)
2-Cl 0 0 3202 Cl H CO(Ph-3,5-F.sub.2) 2-Br 0 0 3203 Cl H
CO(Ph-3,5-F.sub.2) 2-I 0 0 3204 Cl H CO(Ph-3,5-F.sub.2) 2-Me 0 0
3205 Cl H CO(Ph-3,5-F.sub.2) 2-iPr 0 0 3206 Cl H CO(Ph-3,5-F.sub.2)
2-cPr 0 0 3207 Cl H CO(Ph-3,5-F.sub.2) 2-cBu 0 0 3208 Cl H
CO(Ph-3,5-F.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3209 Cl H
CO(Ph-3,5-F.sub.2) 2-cPr, 5-Me 0 0 3210 Cl H CO(Ph-3,5-F.sub.2)
2-OMe, 5-Me 0 0 3211 Cl H CO(Ph-3,5-F.sub.2) 2-F, 6-iPr 0 0 3212 Cl
H CO(Ph-3,5-F.sub.2) 2-Cl, 6-cPr 0 0 3213 Cl H CO(Ph-3,5-F.sub.2)
2-Br, 6-Me 0 0 3214 Cl H CO(Ph-3,5-F.sub.2) 2-I, 6-Me 0 0 3215 Cl H
CO(Ph-3,5-F.sub.2) 2,6-Me.sub.2 0 0 3216 Cl H CO(Ph-3,5-F.sub.2)
2-Me, 6-Et 0 0 3217 Cl H CO(Ph-3,5-F.sub.2) 2-Me, 6-cPr 0 0 3218 Cl
H CO(Ph-3,5-F.sub.2) 2,6-cPr.sub.2 0 0 3219 Cl H CO(Ph-3,5-F.sub.2)
2-cPr, 3,5-Me.sub.2 0 0 3220 Cl H CO(Ph-3,5-F.sub.2) 2-cPr,
3,6-Me.sub.2 0 0 3221 Cl H CO(Ph-3,5-Cl.sub.2) 2-Me 0 0 3222 Cl H
CO(Ph-3,5-Cl.sub.2) 2-iPr 0 0 3223 Cl H CO(Ph-3,5-Cl.sub.2) 2-cPr 0
0 3224 Cl H CO(Ph-3,5-Cl.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3225 Cl H CO(Ph-3,5-Cl.sub.2) 2,6-Me.sub.2 0 0 3226 Cl H
CO(Ph-3,5-Cl.sub.2) 2-Me, 6-cPr 0 0 3227 Cl H CO(Ph-3,5-Me.sub.2)
2-Cl 0 0 3228 Cl H CO(Ph-3,5-Me.sub.2) 2-Br 0 0 3229 Cl H
CO(Ph-3,5-Me.sub.2) 2-I 0 0 3230 Cl H CO(Ph-3,5-Me.sub.2) 2-Me 0 0
3231 Cl H CO(Ph-3,5-Me.sub.2) 2-iPr 0 0 3232 Cl H
CO(Ph-3,5-Me.sub.2) 2-cPr 0 0 3233 Cl H CO(Ph-3,5-Me.sub.2) 2-cBu 0
0 3234 Cl H CO(Ph-3,5-Me.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3235 Cl H CO(Ph-3,5-Me.sub.2) 2-cPr, 5-Me 0 0 3236 Cl H
CO(Ph-3,5-Me.sub.2) 2-OMe, 5-Me 0 0 3237 Cl H CO(Ph-3,5-Me.sub.2)
2-F, 6-iPr 0 0 3238 Cl H CO(Ph-3,5-Me.sub.2) 2-Cl, 6-cPr 0 0 3239
Cl H CO(Ph-3,5-Me.sub.2) 2-Br, 6-Me 0 0 3240 Cl H
CO(Ph-3,5-Me.sub.2) 2-I, 6-Me 0 0 3241 Cl H CO(Ph-3,5-Me.sub.2)
2,6-Me.sub.2 0 0 3242 Cl H CO(Ph-3,5-Me.sub.2) 2-Me, 6-Et 0 0 3243
Cl H CO(Ph-3,5-Me.sub.2) 2-Me, 6-cPr 0 0
3244 Cl H CO(Ph-3,5-Me.sub.2) 2,6-cPr.sub.2 0 0 3245 Cl H
CO(Ph-3,5-Me.sub.2) 2-cPr, 3,5-Me.sub.2 0 0 3246 Cl H
CO(Ph-3,5-Me.sub.2) 2-cPr, 3,6-Me.sub.2 0 0 3247 Cl H
CO{Ph-3,5-(OMe).sub.2} 2-Me 0 0 3248 Cl H CO{Ph-3,5-(OMe).sub.2}
2-iPr 0 0 3249 Cl H CO{Ph-3,5-(OMe).sub.2} 2-cPr 0 0 3250 Cl H
CO{Ph-3,5-(OMe).sub.2} 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3251 Cl H
CO{Ph-3,5-(OMe).sub.2} 2,6-Me.sub.2 0 0 3252 Cl H
CO{Ph-3,5-(OMe).sub.2} 2-Me, 6-cPr 0 0 3253 Cl H
CO(Ph-2,4,6-Cl.sub.3) 2-Me 0 0 3254 Cl H CO(Ph-2,4,6-Cl.sub.3)
2-iPr 0 0 3255 Cl H CO(Ph-2,4,6-Cl.sub.3) 2-cPr 0 0 3256 Cl H
CO(Ph-2,4,6-Cl.sub.3) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3257 Cl H
CO(Ph-2,4,6-Cl.sub.3) 2,6-Me.sub.2 0 0 3258 Cl H
CO(Ph-2,4,6-Cl.sub.3) 2-Me, 6-cPr 0 0 3259 Cl H
CO{Ph-3,4,5-(OMe).sub.3} 2-Me 0 0 3260 Cl H
CO{Ph-3,4,5-(OMe).sub.3} 2-iPr 0 0 3261 Cl H
CO{Ph-3,4,5-(OMe).sub.3} 2-cPr 0 0 3262 Cl H
CO{Ph-3,4,5-(OMe).sub.3} 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3263 Cl H
CO{Ph-3,4,5-(OMe).sub.3} 2,6-Me.sub.2 0 0 3264 Cl H
CO{Ph-3,4,5-(OMe).sub.3} 2-Me, 6-cPr 0 0 3265 Cl H CO(1-Np) 2-Me 0
0 3266 Cl H CO(1-Np) 2-iPr 0 0 3267 Cl H CO(1-Np) 2-cPr 0 0 3268 Cl
H CO(1-Np) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3269 Cl H CO(1-Np)
2,6-Me.sub.2 0 0 3270 Cl H CO(1-Np) 2-Me, 6-cPr 0 0 3271 Cl H
CO(2-Np) 2-Me 0 0 3272 Cl H CO(2-Np) 2-iPr 0 0 3273 Cl H CO(2-Np)
2-cPr 0 0 3274 Cl H CO(2-Np) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3275
Cl H CO(2-Np) 2,6-Me.sub.2 0 0 3276 Cl H CO(2-Np) 2-Me, 6-cPr 0 0
3277 Cl H CO(2-Pyrr-1-Me) 2-Me 0 0 3278 Cl H CO(2-Pyrr-1-Me) 2-iPr
0 0 3279 Cl H CO(2-Pyrr-1-Me) 2-cPr 0 0 3280 Cl H CO(2-Pyrr-1-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3281 Cl H CO(2-Pyrr-1-Me)
2,6-Me.sub.2 0 0 3282 Cl H CO(2-Pyrr-1-Me) 2-Me, 6-cPr 0 0 3283 Cl
H CO(2-Fur-5-Br) 2-Me 0 0 3284 Cl H CO(2-Fur-5-Br) 2-iPr 0 0 3285
Cl H CO(2-Fur-5-Br) 2-cPr 0 0 3286 Cl H CO(2-Fur-5-Br)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3287 Cl H CO(2-Fur-5-Br)
2,6-Me.sub.2 0 0 3288 Cl H CO(2-Fur-5-Br) 2-Me, 6-cPr 0 0 3289 Cl H
CO(3-Fur) 2-Me 0 0 3290 Cl H CO(3-Fur) 2-iPr 0 0 3291 Cl H
CO(3-Fur) 2-cPr 0 0 3292 Cl H CO(3-Fur)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3293 Cl H CO(3-Fur) 2,6-Me.sub.2 0
0 3294 Cl H CO(3-Fur) 2-Me, 6-cPr 0 0 3295 Cl H
CO(3-Fur-2-Me-5-tBu) 2-Me 0 0 3296 Cl H CO(3-Fur-2-Me-5-tBu) 2-iPr
0 0 3297 Cl H CO(3-Fur-2-Me-5-tBu) 2-cPr 0 0 3298 Cl H
CO(3-Fur-2-Me-5-tBu) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3299 Cl H
CO(3-Fur-2-Me-5-tBu) 2,6-Me.sub.2 0 0 3300 Cl H
CO(3-Fur-2-Me-5-tBu) 2-Me, 6-cPr 0 0 3301 Cl H
CO(3-Fur-2-CF.sub.3-5-Me) 2-Me 0 0 3302 Cl H
CO(3-Fur-2-CF.sub.3-5-Me) 2-iPr 0 0 3303 Cl H
CO(3-Fur-2-CF.sub.3-5-Me) 2-cPr 0 0 3304 Cl H
CO(3-Fur-2-CF.sub.3-5-Me) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3305 Cl
H CO(3-Fur-2-CF.sub.3-5-Me) 2,6-Me.sub.2 0 0 3306 Cl H
CO(3-Fur-2-CF.sub.3-5-Me) 2-Me, 6-cPr 0 0 3307 Cl H
CO{3-Fur-2-CF.sub.3-5-(Ph-4-Cl)} 2-Me 0 0 3308 Cl H
CO{3-Fur-2-CF.sub.3-5-(Ph-4-Cl)} 2-iPr 0 0 3309 Cl H
CO{3-Fur-2-CF.sub.3-5-(Ph-4-Cl)} 2-cPr 0 0 3310 Cl H
CO{3-Fur-2-CF.sub.3-5-(Ph-4-Cl)} 2-CH.sub.2CH.sub.2CH.sub.2-3 0 - 0
3311 Cl H CO{3-Fur-2-CF.sub.3-5-(Ph-4-Cl)} 2,6-Me.sub.2 0 0 3312 Cl
H CO{3-Fur-2-CF.sub.3-5-(Ph-4-Cl)} 2-Me, 6-cPr 0 0 3313 Cl H
CO(2-Thi-3-Cl) 2-Me 0 0 3314 Cl H CO(2-Thi-3-Cl) 2-iPr 0 0 3315 Cl
H CO(2-Thi-3-Cl) 2-cPr 0 0 3316 Cl H CO(2-Thi-3-Cl)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3317 Cl H CO(2-Thi-3-Cl)
2,6-Me.sub.2 0 0 3318 Cl H CO(2-Thi-3-Cl) 2-Me, 6-cPr 0 0 3319 Cl H
CO(2-Thi-3-Me) 2-Me 0 0 3320 Cl H CO(2-Thi-3-Me) 2-iPr 0 0 3321 Cl
H CO(2-Thi-3-Me) 2-cPr 0 0 3322 Cl H CO(2-Thi-3-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3323 Cl H CO(2-Thi-3-Me)
2,6-Me.sub.2 0 0 3324 Cl H CO(2-Thi-3-Me) 2-Me, 6-cPr 0 0 3325 Cl H
CO(2-Thi-3-OEt) 2-Me 0 0 3326 Cl H CO(2-Thi-3-OEt) 2-iPr 0 0 3327
Cl H CO(2-Thi-3-OEt) 2-cPr 0 0 3328 Cl H CO(2-Thi-3-OEt)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3329 Cl H CO(2-Thi-3-OEt)
2,6-Me.sub.2 0 0 3330 Cl H CO(2-Thi-3-OEt) 2-Me, 6-cPr 0 0 3331 Cl
H CO(2-Thi-5-Cl) 2-Me 0 0 3332 Cl H CO(2-Thi-5-Cl) 2-iPr 0 0 3333
Cl H CO(2-Thi-5-Cl) 2-cPr 0 0 3334 Cl H CO(2-Thi-5-Cl)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3335 Cl H CO(2-Thi-5-Cl)
2,6-Me.sub.2 0 0 3336 Cl H CO(2-Thi-5-Cl) 2-Me, 6-cPr 0 0 3337 Cl H
CO(2-Thi-5-Br) 2-Me 0 0 3338 Cl H CO(2-Thi-5-Br) 2-iPr 0 0 3339 Cl
H CO(2-Thi-5-Br) 2-cPr 0 0 3340 Cl H CO(2-Thi-5-Br)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3341 Cl H CO(2-Thi-5-Br)
2,6-Me.sub.2 0 0 3342 Cl H CO(2-Thi-5-Br) 2-Me, 6-cPr 0 0 3343 Cl H
CO(2-Thi-5-Me) 2-Me 0 0 3344 Cl H CO(2-Thi-5-Me) 2-iPr 0 0 3345 Cl
H CO(2-Thi-5-Me) 2-cPr 0 0 3346 Cl H CO(2-Thi-5-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3347 Cl H CO(2-Thi-5-Me)
2,6-Me.sub.2 0 0 3348 Cl H CO(2-Thi-5-Me) 2-Me, 6-cPr 0 0 3349 Cl H
CO(2-Thi-5-COMe) 2-Me 0 0 3350 Cl H CO(2-Thi-5-COMe) 2-iPr 0 0 3351
Cl H CO(2-Thi-5-COMe) 2-cPr 0 0 3352 Cl H CO(2-Thi-5-COMe)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3353 Cl H CO(2-Thi-5-COMe)
2,6-Me.sub.2 0 0 3354 Cl H CO(2-Thi-5-COMe) 2-Me, 6-cPr 0 0 3355 Cl
H CO(3-Thi-5-NO.sub.2) 2-Me 0 0 3356 Cl H CO(3-Thi-5-NO.sub.2)
2-iPr 0 0 3357 Cl H CO(3-Thi-5-NO.sub.2) 2-cPr 0 0 3358 Cl H
CO(3-Thi-5-NO.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3359 Cl H
CO(3-Thi-5-NO.sub.2) 2,6-Me.sub.2 0 0 3360 Cl H
CO(3-Thj-5-NO.sub.2) 2-Me, 6-cPr 0 0 3361 Cl H
CO(2-Thi-4,5-Br.sub.2) 2-Me 0 0 3362 Cl H CO(2-Thi-4,5-Br.sub.2)
2-iPr 0 0 3363 Cl H CO(2-Thi-4,5-Br.sub.2) 2-cPr 0 0 3364 Cl H
CO(2-Thi-4,5-Br.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3365 Cl H
CO(2-Thi-4,5-Br.sub.2) 2,6-Me.sub.2 0 0 3366 Cl H
CO(2-Thi-4,5-Br.sub.2) 2-Me, 6-cPr 0 0 3367 Cl H CO(3-Thi) 2-Me 0 0
3368 Cl H CO(3-Thi) 2-iPr 0 0 3369 Cl H CO(3-Thi) 2-cPr 0 0 3370 Cl
H CO(3-Thi) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3371 Cl H CO(3-Thi)
2,6-Me.sub.2 0 0 3372 Cl H CO(3-Thi) 2-Me, 6-cPr 0 0 3373 Cl H
CO(3-Thi-4-OMe) 2-Me 0 0 3374 Cl H CO(3-Thi-4-OMe) 2-iPr 0 0 3375
Cl H CO(3-Thi-4-OMe) 2-cPr 0 0 3376 Cl H CO(3-Thi-4-OMe)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3377 Cl H CO(3-Thi-4-OMe)
2,6-Me.sub.2 0 0 3378 Cl H CO(3-Thi-4-OMe) 2-Me, 6-cPr 0 0 3379 Cl
H CO(5-Pyza-1-CH.sub.2Ph-3-tBu) 2-Me 0 0 3380 Cl H
CO(5-Pyza-1-CH.sub.2Ph-3-tBu) 2-iPr 0 0 3381 Cl H
CO(5-Pyza-1-CH.sub.2Ph-3-tBu) 2-cPr 0 0 3382 Cl H
CO(5-Pyza-1-CH.sub.2Ph-3-tBu) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3383
Cl H CO(5-Pyza-1-CH.sub.2Ph-3-tBu) 2,6-Me.sub.2 0 0 3384 Cl H
CO(5-Pyza-1-CH.sub.2Ph-3-tBu) 2-Me, 6-cPr 0 0 3385 Cl H
CO(4-Pyza-1,3-Me.sub.2-5-Cl) 2-Me 0 0 3386 Cl H
CO(4-Pyza-1,3-Me.sub.2-5-Cl) 2-iPr 0 0 3387 Cl H
CO(4-Pyza-1,3-Me.sub.2-5-Cl) 2-cPr 0 0 3388 Cl H
CO(4-Pyza-1,3-Me.sub.2-5-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3389
Cl H CO(4-Pyza-1,3-Me.sub.2-5-Cl) 2,6-Me.sub.2 0 0 3390 Cl H
CO(4-Pyza-1,3-Me.sub.2-5-Cl) 2-Me, 6-cPr 0 0 3391 Cl H
CO{4-Ioxa-5-Me-3-(Ph-2-Cl)} 2-Me 0 0 3392 Cl H
CO{4-Ioxa-5-Me-3-(Ph-2-Cl)} 2-iPr 0 0 3393 Cl H
CO{4-Ioxa-5-Me-3-(Ph-2-Cl)} 2-cPr 0 0 3394 Cl H
CO{4-Ioxa-5-Me-3-(Ph-2-Cl)} 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3395
Cl H CO{4-Ioxa-5-Me-3-(Ph-2-Cl)} 2,6-Me.sub.2 0 0 3396 Cl H
CO{4-Ioxa-5-Me-3-(Ph-2-Cl)} 2-Me, 6-cPr 0 0 3397 Cl H
CO(5-Tdia-4-Me) 2-Me 0 0 3398 Cl H CO(5-Tdia-4-Me) 2-iPr 0 0 3399
Cl H CO(5-Tdia-4-Me) 2-cPr 0 0 3400 Cl H CO(5-Tdia-4-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3401 Cl H CO(5-Tdia-4-Me)
2,6-Me.sub.2 0 0 3402 Cl H CO(5-Tdia-4-Me) 2-Me, 6-cPr 0 0 3403 Cl
H CO(2-Pyr-6-Me) 2-Me 0 0 3404 Cl H CO(2-Pyr-6-Me) 2-iPr 0 0 3405
Cl H CO(2-Pyr-6-Me) 2-cPr 0 0 3406 Cl H CO(2-Pyr-6-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3407 Cl H CO(2-Pyr-6-Me)
2,6-Me.sub.2 0 0 3408 Cl H CO(2-Pyr-6-Me) 2-Me, 6-cPr 0 0 3409 Cl H
CO(2-Pyr-5-Bu) 2-Me 0 0 3410 Cl H CO(2-Pyr-5-Bu) 2-iPr 0 0 3411 Cl
H CO(2-Pyr-5-Bu) 2-cPr 0 0 3412 Cl H CO(2-Pyr-5-Bu)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3413 Cl H CO(2-Pyr-5-Bu)
2,6-Me.sub.2 0 0 3414 Cl H CO(2-Pyr-5-Bu) 2-Me, 6-cPr 0 0 3415 Cl H
CO(3-Pyr) 2-Me 0 0 3416 Cl H CO(3-Pyr) 2-iPr 0 0 3417 Cl H
CO(3-Pyr) 2-cPr 0 0 3418 Cl H CO(3-Pyr)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3419 Cl H CO(3-Pyr) 2,6-Me.sub.2 0
0 3420 Cl H CO(3-Pyr) 2-Me, 6-cPr 0 0 3421 Cl H CO(3-Pyr-2-Cl) 2-Me
0 0 3422 Cl H CO(3-Pyr-2-Cl) 2-iPr 0 0 3423 Cl H CO(3-Pyr-2-Cl)
2-cPr 0 0 3424 Cl H CO(3-Pyr-2-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3425 Cl H CO(3-Pyr-2-Cl) 2,6-Me.sub.2 0 0 3426 Cl H CO(3-Pyr-2-Cl)
2-Me, 6-cPr 0 0 3427 Cl H CO(3-Pyr-2-Me) 2-Me 0 0 3428 Cl H
CO(3-Pyr-2-Me) 2-iPr 0 0 3429 Cl H CO(3-Pyr-2-Me) 2-cPr 0 0 3430 Cl
H CO(3-Pyr-2-Me) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3431 Cl H
CO(3-Pyr-2-Me) 2,6-Me.sub.2 0 0 3432 Cl H CO(3-Pyr-2-Me) 2-Me,
6-cPr 0 0 3433 Cl H CO(3-Pyr-2-OPh) 2-Me 0 0 3434 Cl H
CO(3-Pyr-2-OPh) 2-iPr 0 0 3435 Cl H CO(3-Pyr-2-OPh) 2-cPr 0 0 3436
Cl H CO(3-Pyr-2-OPh) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3437 Cl H
CO(3-Pyr-2-OPh) 2,6-Me.sub.2 0 0 3438 Cl H CO(3-Pyr-2-OPh) 2-Me,
6-cPr 0 0 3439 Cl H CO(3-Pyr-2-SMe) 2-Me 0 0 3440 Cl H
CO(3-Pyr-2-SMe) 2-iPr 0 0 3441 Cl H CO(3-Pyr-2-SMe) 2-cPr 0 0 3442
Cl H CO(3-Pyr-2-SMe) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3443 Cl H
CO(3-Pyr-2-SMe) 2,6-Me.sub.2 0 0 3444 Cl H CO(3-Pyr-2-SMe) 2-Me,
6-cPr 0 0 3445 Cl H CO(3-Pyr-2-SCH.sub.2CH.dbd.CH.sub.2) 2-Me 0 0
3446 Cl H CO(3-Pyr-2-SCH.sub.2CH.dbd.CH.sub.2) 2-iPr 0 0 3447 Cl H
CO(3-Pyr-2-SCH.sub.2CH.dbd.CH.sub.2) 2-cPr 0 0 3448 Cl H
CO(3-Pyr-2-SCH.sub.2CH.dbd.CH.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-- 3
0 0 3449 Cl H CO(3-Pyr-2-SCH.sub.2CH.dbd.CH.sub.2) 2,6-Me.sub.2 0 0
3450 Cl H CO(3-Pyr-2-SCH.sub.2CH.dbd.CH.sub.2) 2-Me, 6-cPr 0 0 3451
Cl H CO(3-Pyr-2-SPh) 2-Me 0 0 3452 Cl H CO(3-Pyr-2-SPh) 2-iPr 0 0
3453 Cl H CO(3-Pyr-2-SPh) 2-cPr 0 0 3454 Cl H CO(3-Pyr-2-SPh)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3455 Cl H CO(3-Pyr-2-SPh)
2,6-Me.sub.2 0 0 3456 Cl H CO(3-Pyr-2-SPh) 2-Me, 6-cPr 0 0 3457 Cl
H CO(3-Pyr-4-CF.sub.3) 2-Me 0 0 3458 Cl H CO(3-Pyr-4-CF.sub.3)
2-iPr 0 0 3459 Cl H CO(3-Pyr-4-CF.sub.3) 2-cPr 0 0 3460 Cl H
CO(3-Pyr-4-CF.sub.3) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3461 Cl H
CO(3-Pyr-4-CF.sub.3) 2,6-Me.sub.2 0 0 3462 Cl H
CO(3-Pyr-4-CF.sub.3) 2-Me, 6-cPr 0 0 3463 Cl H CO(3-Pyr-6-Cl) 2-Me
0 0 3464 Cl H CO(3-Pyr-6-Cl) 2-iPr 0 0 3465 Cl H CO(3-Pyr-6-Cl)
2-cPr 0 0 3466 Cl H CO(3-Pyr-6-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3467 Cl H CO(3-Pyr-6-Cl) 2,6-Me.sub.2 0 0 3468 Cl H CO(3-Pyr-6-Cl)
2-Me, 6-cPr 0 0 3469 Cl H CO(3-Pyr-2,6-Cl.sub.2) 2-Me 0 0 3470 Cl H
CO(3-Pyr-2,6-Cl.sub.2) 2-iPr 0 0 3471 Cl H CO(3-Pyr-2,6-Cl.sub.2)
2-cPr 0 0 3472 Cl H CO(3-Pyr-2,6-Cl.sub.2)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3473 Cl H CO(3-Pyr-2,6-Cl.sub.2)
2,6-Me.sub.2 0 0 3474 Cl H CO(3-Pyr-2,6-Cl.sub.2) 2-Me, 6-cPr 0 0
3475 Cl H CO(3-Pyr-2-Cl-6-Me) 2-Me 0 0 3476 Cl H
CO(3-Pyr-2-Cl-6-Me) 2-iPr 0 0 3477 Cl H CO(3-Pyr-2-Cl-6-Me) 2-cPr 0
0 3478 Cl H CO(3-Pyr-2-Cl-6-Me) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3479 Cl H CO(3-Pyr-2-Cl-6-Me) 2,6-Me.sub.2 0 0 3480 Cl H
CO(3-Pyr-2-Cl-6-Me) 2-Me, 6-cPr 0 0 3481 Cl H
CO(3-Pyr-5,6-Cl.sub.2) 2-Me 0 0 3482 Cl H CO(3-Pyr-5,6-Cl.sub.2)
2-iPr 0 0 3483 Cl H CO(3-Pyr-5,6-Cl.sub.2) 2-cPr 0 0 3484 Cl H
CO(3-Pyr-5,6-Cl.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3485 Cl H
CO(3-Pyr-5,6-Cl.sub.2) 2,6-Me.sub.2 0 0 3486 Cl H
CO(3-Pyr-5,6-Cl.sub.2) 2-Me, 6-cPr 0 0 3487 Cl H CO(4-Pyr-2-Cl)
2-Me 0 0 3488 Cl H CO(4-Pyr-2-Cl) 2-iPr 0 0 3489 Cl H
CO(4-Pyr-2-Cl) 2-cPr 0 0 3490 Cl H CO(4-Pyr-2-Cl)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3491 Cl H CO(4-Pyr-2-Cl)
2,6-Me.sub.2 0 0 3492 Cl H CO(4-Pyr-2-Cl) 2-Me, 6-cPr 0 0
3493 Cl H CO(2-Bfur) 2-Me 0 0 3494 Cl H CO(2-Bfur) 2-iPr 0 0 3495
Cl H CO(2-Bfur) 2-cPr 0 0 3496 Cl H CO(2-Bfur)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3497 Cl H CO(2-Bfur) 2,6-Me.sub.2
0 0 3498 Cl H CO(2-Bfur) 2-Me, 6-cPr 0 0 3499 Cl H CO(2-Bthi) 2-Me
0 0 3500 Cl H CO(2-Bthi) 2-iPr 0 0 3501 Cl H CO(2-Bthi) 2-cPr 0 0
3502 Cl H CO(2-Bthi) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3503 Cl H
CO(2-Bthi) 2,6-Me.sub.2 0 0 3504 Cl H CO(2-Bthi) 2-Me, 6-cPr 0 0
3505 Cl H CO(6-Bthia) 2-Me 0 0 3506 Cl H CO(6-Bthia) 2-iPr 0 0 3507
Cl H CO(6-Bthia) 2-cPr 0 0 3508 Cl H CO(6-Bthia)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3509 Cl H CO(6-Bthia) 2,6-Me.sub.2
0 0 3510 Cl H CO(6-Bthia) 2-Me, 6-cPr 0 0 3511 Cl H CO(5-Boxaz)
2-Me 0 0 3512 Cl H CO(5-Boxaz) 2-iPr 0 0 3513 Cl H CO(5-Boxaz)
2-cPr 0 0 3514 Cl H CO(5-Boxaz) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3515 Cl H CO(5-Boxaz) 2,6-Me.sub.2 0 0 3516 Cl H CO(5-Boxaz) 2-Me,
6-cPr 0 0 3517 Cl H CO(1-Iqu) 2-Me 0 0 3518 Cl H CO(1-Iqu) 2-iPr 0
0 3519 Cl H CO(1-Iqu) 2-cPr 0 0 3520 Cl H CO(1-Iqu)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3521 Cl H CO(1-Iqu) 2,6-Me.sub.2 0
0 3522 Cl H CO(1-Iqu) 2-Me, 6-cPr 0 0 3523 Cl H CONMe(tBu) 2-Me 0 0
3524 Cl H CONMe(tBu) 2-iPr 0 0 3525 Cl H CONMe(tBu) 2-cPr 0 0 3526
Cl H CONMe(tBu) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3527 Cl H
CONMe(tBu) 2,6-Me.sub.2 0 0 3528 Cl H CONMe(tBu) 2-Me, 6-cPr 0 0
3529 Cl H CONBu.sub.2 2-Me 0 0 3530 Cl H CONBu.sub.2 2-iPr 0 0 3531
Cl H CONBu.sub.2 2-cPr 0 0 3532 Cl H CONBu.sub.2
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3533 Cl H CONBu.sub.2 2,6-Me.sub.2
0 0 3534 Cl H CONBu.sub.2 2-Me, 6-cPr 0 0 3535 Cl H
CONMe(CH.sub.2Ph) 2-Me 0 0 3536 Cl H CONMe(CH.sub.2Ph) 2-iPr 0 0
3537 Cl H CONMe(CH.sub.2Ph) 2-cPr 0 0 3538 Cl H CONMe(CH.sub.2Ph)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3539 Cl H CONMe(CH.sub.2Ph)
2,6-Me.sub.2 0 0 3540 Cl H CONMe(CH.sub.2Ph) 2-Me, 6-cPr 0 0 3541
Cl H CONMe(CH.sub.2CN) 2-Me 0 0 3542 Cl H CONMe(CH.sub.2CN) 2-iPr 0
0 3543 Cl H CONMe(CH.sub.2CN) 2-cPr 0 0 3544 Cl H CONMe(CH.sub.2CN)
2CH.sub.2CH.sub.2CH.sub.2-3 0 0 3545 Cl H CONMe(CH.sub.2CN)
2,6-Me.sub.2 0 0 3546 Cl H CONMe(CH.sub.2CN) 2-Me, 6-cPr 0 0 3547
Cl H CONMe(CH.sub.2CO.sub.2Et) 2-Me 0 0 3548 Cl H
CONMe(CH.sub.2CO.sub.2Et) 2-iPr 0 0 3549 Cl H
CONMe(CH.sub.2CO.sub.2Et) 2-cPr 0 0 3550 Cl H
CONMe(CH.sub.2CO.sub.2Et) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3551 Cl
H CONMe(CH.sub.2CO.sub.2Et) 2,6-Me.sub.2 0 0 3552 Cl H
CONMe(CH.sub.2CO.sub.2Et) 2-Me, 6-cPr 0 0 3553 Cl H CONMe(2-Pyr)
2-Me 0 0 3554 Cl H CONMe(2-Pyr) 2-iPr 0 0 3555 Cl H CONMe(2-Pyr)
2-cPr 0 0 3556 Cl H CONMe(2-Pyr) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3557 Cl H CONMe(2-Pyr) 2,6-Me.sub.2 0 0 3558 Cl H CONMe(2-Pyr)
2-Me, 6-cPr 0 0 3559 Cl H CONMe(OMe) 2-Me 0 0 3560 Cl H CONMe(OMe)
2-iPr 0 0 3561 Cl H CONMe(OMe) 2-cPr 0 0 3562 Cl H CONMe(OMe)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3563 Cl H CONMe(OMe) 2,6-Me.sub.2
0 0 3564 Cl H CONMe(OMe) 2-Me, 6-cPr 0 0 3565 Cl H
CON(CH.sub.2CH.sub.2Cl).sub.2 2-Me 0 0 3566 Cl H
CON(CH.sub.2CH.sub.2Cl).sub.2 2-iPr 0 0 3567 Cl H
CON(CH.sub.2CH.sub.2Cl).sub.2 2-cPr 0 0 3568 Cl H
CON(CH.sub.2CH.sub.2Cl).sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3569
Cl H CON(CH.sub.2CH.sub.2Cl).sub.2 2,6-Me.sub.2 0 0 3570 Cl H
CON(CH.sub.2CH.sub.2Cl).sub.2 2-Me, 6-cPr 0 0 3571 Cl H
CON(CH.sub.2CH.dbd.CH.sub.2).sub.2 2-Me 0 0 3572 Cl H
CON(CH.sub.2CH.dbd.CH.sub.2).sub.2 2-iPr 0 0 3573 Cl H
CON(CH.sub.2CH.dbd.CH.sub.2).sub.2 2-cPr 0 0 3574 Cl H
CON(CH.sub.2CH.dbd.CH.sub.2).sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 - 0
0 3575 Cl H CON(CH.sub.2CH.dbd.CH.sub.2).sub.2 2,6-Me.sub.2 0 0
3576 Cl H CON(CH.sub.2CH.dbd.CH.sub.2).sub.2 2-Me, 6-cPr 0 0 3577
Cl H CON(CH.sub.2CN).sub.2 2-Me 0 0 3578 Cl H CON(CH.sub.2CN).sub.2
2-iPr 0 0 3579 Cl H CON(CH.sub.2CN).sub.2 2-cPr 0 0 3580 Cl H
CON(CH.sub.2CN).sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3581 Cl H
CON(CH.sub.2CN).sub.2 2,6-Me.sub.2 0 0 3582 Cl H
CON(CH.sub.2CN).sub.2 2-Me, 6-cPr 0 0 3583 Cl H
CON(CH.sub.2CH.sub.2CN).sub.2 2-Me 0 0 3584 Cl H
CON(CH.sub.2CH.sub.2CN).sub.2 2-iPr 0 0 3585 Cl H
CON(CH.sub.2CH.sub.2CN).sub.2 2-cPr 0 0 3586 Cl H
CON(CH.sub.2CH.sub.2CN).sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3587
Cl H CON(CH.sub.2CH.sub.2CN).sub.2 2,6-Me.sub.2 0 0 3588 Cl H
CON(CH.sub.2CH.sub.2CN).sub.2 2-Me, 6-cPr 0 0 3589 Cl H
CON(CH.sub.2CO.sub.2Et).sub.2 2-Me 0 0 3590 Cl H
CON(CH.sub.2CO.sub.2Et).sub.2 2-iPr 0 0 3591 Cl H
CON(CH.sub.2CO.sub.2Et).sub.2 2-cPr 0 0 3592 Cl H
CON(CH.sub.2cO.sub.2Et).sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3593
Cl H CON(CH.sub.2CO.sub.2Et).sub.2 2,6-Me.sub.2 0 0 3594 Cl H
CON(CH.sub.2CO.sub.2Et).sub.2 2-Me, 6-cPr 0 0 3595 Cl H
CON(CH.sub.2CH.sub.2OMe).sub.2 2-Me 0 0 3596 Cl H
CON(CH.sub.2CH.sub.2OMe).sub.2 2-iPr 0 0 3597 Cl H
CON(CH.sub.2CH.sub.2OMe).sub.2 2-cPr 0 0 3598 Cl H
CON(CH.sub.2CH.sub.2OMe).sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3599 Cl H CON(CH.sub.2CH.sub.2OMe).sub.2 2,6-Me.sub.2 0 0 3600 Cl H
CON(CH.sub.2CH.sub.2OMe).sub.2 2-Me, 6-cPr 0 0 3601 Cl H
CON(CH.sub.2CH.sub.2OEt).sub.2 2-Me 0 0 3602 Cl H
CON(CH.sub.2CH.sub.2OEt).sub.2 2-iPr 0 0 3603 Cl H
CON(CH.sub.2CH.sub.2OEt).sub.2 2-cPr 0 0 3604 Cl H
CON(CH.sub.2CH.sub.2OEt).sub.2 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3605 Cl H CON(CH.sub.2CH.sub.2OEt).sub.2 2,6-Me.sub.2 0 0 3606 Cl H
CON(CH.sub.2CH.sub.2OEt).sub.2 2-Me, 6-cPr 0 0 3607 Cl H CO(1-Azet)
2-Me 0 0 3608 Cl H CO(1-Azet) 2-iPr 0 0 3609 Cl H CO(1-Azet) 2-cPr
0 0 3610 Cl H CO(1-Azet) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3611 Cl H
CO(1-Azet) 2,6-Me.sub.2 0 0 3612 Cl H CO(1-Azet) 2-Me, 6-cPr 0 0
3613 Cl H CO(1-Pyrd-2-CO.sub.2Me) 2-Me 0 0 3614 Cl H
CO(1-Pyrd-2-CO.sub.2Me) 2-iPr 0 0 3615 Cl H CO(1-Pyrd-2-CO.sub.2Me)
2-cPr 0 0 3616 Cl H CO(1-Pyrd-2-CO.sub.2Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3617 Cl H CO(1-Pyrd-2-CO.sub.2Me)
2,6-Me.sub.2 0 0 3618 Cl H CO(1-Pyrd-2-CO.sub.2Me) 2-Me, 6-cPr 0 0
3619 Cl H CO(1-Pyrd-3-OH) 2-Me 0 0 3620 Cl H CO(1-Pyrd-3-OH) 2-iPr
0 0 3621 Cl H CO(1-Pyrd-3-OH) 2-cPr 0 0 3622 Cl H CO(1-Pyrd-3-OH)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3623 Cl H CO(1-Pyrd-3-OH)
2,6-Me.sub.2 0 0 3624 Cl H CO(1-Pyrd-3-OH) 2-Me, 6-cPr 0 0 3625 Cl
H CO(1-Pyrr-2,5-Me.sub.2) 2-Me 0 0 3626 Cl H
CO(1-Pyrr-2,5-Me.sub.2) 2-iPr 0 0 3627 Cl H CO(1-Pyrr-2,5-Me.sub.2)
2-cPr 0 0 3628 Cl H CO(1-Pyrr-2,5-Me.sub.2)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3629 Cl H CO(1-Pyrr-2,5-Me.sub.2)
2,6-Me.sub.2 0 0 3630 Cl H CO(1-Pyrr-2,5-Me.sub.2) 2-Me, 6-cPr 0 0
3631 Cl H CO(1-Ppri) 2-Me 0 0 3632 Cl H CO(1-Ppri) 2-iPr 0 0 3633
Cl H CO(1-Ppri) 2-cPr 0 0 3634 Cl H CO(1-Ppri)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3635 Cl H CO(1-Ppri) 2,6-Me.sub.2
0 0 3636 Cl H CO(1-Ppri) 2-Me, 6-cPr 0 0 3637 Cl H
CO(1-Ppri-2-CO.sub.2Me) 2-Me 0 0 3638 Cl H CO(1-Ppri-2-CO.sub.2Me)
2-iPr 0 0 3639 Cl H CO(1-Ppri-2-CO.sub.2Me) 2-cPr 0 0 3640 Cl H
CO(1-Ppri-2-CO.sub.2Me) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3641 Cl H
CO(1-Ppri-2-CO.sub.2Me) 2,6-Me.sub.2 0 0 3642 Cl H
CO(1-Ppri-2-CO.sub.2Me) 2-Me, 6-cPr 0 0 3643 Cl H CO(1-Ppri-4-Br)
2-Me 0 0 3644 Cl H CO(1-Ppri-4-Br) 2-iPr 0 0 3645 Cl H
CO(1-Ppri-4-Br) 2-cPr 0 0 3646 Cl H CO(1-Ppri-4-Br)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3647 Cl H CO(1-Ppri-4-Br)
2,6-Me.sub.2 0 0 3648 Cl H CO(1-Ppri-4-Br) 2-Me, 6-cPr 0 0 3649 Cl
H CO(1-Ppri-4-Me) 2-Me 0 0 3650 Cl H CO(1-Ppri-4-Me) 2-iPr 0 0 3651
Cl H CO(1-Ppri-4-Me) 2-cPr 0 0 3652 Cl H CO(1-Ppri-4-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3653 Cl H CO(1-Ppri-4-Me)
2,6-Me.sub.2 0 0 3654 Cl H CO(1-Ppri-4-Me) 2-Me, 6-cPr 0 0 3655 Cl
H CO(1-Ppri-4-CO.sub.2Me) 2-Me 0 0 3656 Cl H
CO(1-Ppri-4-CO.sub.2Me) 2-iPr 0 0 3657 Cl H CO(1-Ppri-4-CO.sub.2Me)
2-cPr 0 0 3658 Cl H CO(1-Ppri-4-CO.sub.2Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3659 Cl H CO(1-Ppri-4-CO.sub.2Me)
2,6-Me.sub.2 0 0 3660 Cl H CO(1-Ppri-4-CO.sub.2Et) 2-Me, 6-cPr 0 0
3661 Cl H CO(1-Ppri-4-OCH.sub.2CH.sub.2O-4) 2-Me 0 0 3662 Cl H
CO(1-Ppri-4-OCH.sub.2CH.sub.2O-4) 2-iPr 0 0 3663 Cl H
CO(1-Ppri-4-OCH.sub.2CH.sub.2O-4) 2-cPr 0 0 3664 Cl H
CO(1-Ppri-4-OCH.sub.2CH.sub.2O-4) 2-CH.sub.2CH.sub.2CH.sub.2-3 0- 0
3665 Cl H CO(1-Ppri-4-OCH.sub.2CH.sub.2O-4) 2,6-Me.sub.2 0 0 3666
Cl H CO(1-Ppri-4-OCH.sub.2CH.sub.2O-4) 2-Me, 6-cPr 0 0 3667 Cl H
CO(1-Ppri-2,2,6,6-Me.sub.4) 2-Me 0 0 3668 Cl H
CO(1-Ppri-2,2,6,6-Me.sub.4) 2-iPr 0 0 3669 Cl H
CO(1-Ppri-2,2,6,6-Me.sub.4) 2-cPr 0 0 3670 Cl H
CO(1-Ppri-2,2,6,6-Me.sub.4) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3671
Cl H CO(1-Ppri-2,2,6,6-Me.sub.4) 2,6-Me.sub.2 0 0 3672 Cl H
CO(1-Ppri-2,2,6,6-Me.sub.4) 2-Me, 6-cPr 0 0 3673 Cl H
CO(1-Ppra-4-Me) 2-Me 0 0 3674 Cl H CO(1-Ppra-4-Me) 2-iPr 0 0 3675
Cl H CO(1-Ppra-4-Me) 2-cPr 0 0 3676 Cl H CO(1-Ppra-4-Me)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3677 Cl H CO(1-Ppra-4-Me)
2,6-Me.sub.2 0 0 3678 Cl H CO(1-Ppra-4-Me) 2-Me, 6-cPr 0 0 3679 Cl
H CO(1-Ppra-4-Ph) 2-Me 0 0 3680 Cl H CO(1-Ppra-4-Ph) 2-iPr 0 0 3681
Cl H CO(1-Ppra-4-Ph) 2-cPr 0 0 3682 Cl H CO(1-Ppra-4-Ph)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3683 Cl H CO(1-Ppra-4-Ph)
2,6-Me.sub.2 0 0 3684 Cl H CO(1-Ppra-4-Ph) 2-Me, 6-cPr 0 0 3685 Cl
H CO-4-Morp 2-Me 0 0 3686 Cl H CO-4-Morp 2-iPr 0 0 3687 Cl H
CO-4-Morp 2-cPr 0 0 3688 Cl H CO-4-Morp
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3689 Cl H CO-4-Morp 2,6-Me.sub.2 0
0 3690 Cl H CO-4-Morp 2-Me, 6-cPr 0 0 3691 Cl H
CO(4-Morp-2,6-Me.sub.2) 2-Me 0 0 3692 Cl H CO(4-Morp-2,6-Me.sub.2)
2-iPr 0 0 3693 Cl H CO(4-Morp-2,6-Me.sub.2) 2-cPr 0 0 3694 Cl H
CO(4-Morp-2,6-Me.sub.2) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3695 Cl H
CO(4-Morp-2,6-Me.sub.2) 2,6-Me.sub.2 0 0 3696 Cl H
CO(4-Morp-2,6-Me.sub.2) 2-Me, 6-cPr 0 0 3697 Cl H CO-4-Tmor 2-Me 0
0 3698 Cl H CO-4-Tmor 2-iPr 0 0 3699 Cl H CO-4-Tmor 2-cPr 0 0 3700
Cl H CO-4-Tmor 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3701 Cl H CO-4-Tmor
2,6-Me.sub.2 0 0 3702 Cl H CO-4-Tmor 2-Me, 6-cPr 0 0 3703 Cl H
COQ.sup.18 2-Me 0 0 3704 Cl H COQ.sup.18 2-iPr 0 0 3705 Cl H
COQ.sup.18 2-cPr 0 0 3706 Cl H COQ.sup.18
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3707 Cl H COQ.sup.18 2,6-Me.sub.2
0 0 3708 Cl H COQ.sup.18 2-Me, 6-cPr 0 0 3709 Cl H CO(9-Carb) 2-Me
0 0 3710 Cl H CO(9-Carb) 2-iPr 0 0 3711 Cl H CO(9-Carb) 2-cPr 0 0
3712 Cl H CO(9-Carb) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3713 Cl H
CO(9-Carb) 2,6-Me.sub.2 0 0 3714 Cl H CO(9-Carb) 2-Me, 6-cPr 0 0
3715 Cl H CO(10-Pthia) 2-Me 0 0 3716 Cl H CO(10-Pthia) 2-iPr 0 0
3717 Cl H CO(10-Pthia) 2-cPr 0 0 3718 Cl H CO(10-Pthia)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3719 Cl H CO(10-Pthia)
2,6-Me.sub.2 0 0 3720 Cl H CO(10-Pthia) 2-Me, 6-cPr 0 0 3721 Cl H
SO.sub.2 (Ph-2-CO.sub.2Q.sup.5) 2-Me, 6-cPr 0 0 3722 Cl H SO.sub.2
(Ph-3-CO.sub.2Q.sup.5) 2-Me, 6-cPr 0 0 3723 Cl H SO.sub.2
(Ph-4-CO.sub.2Q.sup.5) 2-Me, 6-cPr 0 0 3724 Cl H SO.sub.2
(Ph-4-OMe) 2-Cl 0 0 3725 Cl H SO.sub.2 (Ph-4-OMe) 2-Br 0 0 3726 Cl
H SO.sub.2 (Ph-4-OMe) 2-I 0 0 3727 Cl H SO.sub.2 (Ph-4-OMe) 2-cBu 0
0 3728 Cl H SO.sub.2 (Ph-4-OMe) 2-cPr, 5-Me 0 0 3729 Cl H SO.sub.2
(Ph-4-OMe) 2-OMe, 5-Me 0 0 3730 Cl H SO.sub.2 (Ph-4-OMe) 2-F, 6-iPr
0 0 3731 Cl H SO.sub.2 (Ph-4-OMe) 2-Cl, 6-cPr 0 0 3732 Cl H
SO.sub.2 (Ph-4-OMe) 2-Br, 6-Me 0 0 3733 Cl H SO.sub.2 (Ph-4-OMe)
2-I, 6-Me 0 0 3734 Cl H SO.sub.2 (Ph-4-OMe) 2-Me, 6-Et 0 0 3735 Cl
H SO.sub.2 (Ph-4-OMe) 2,6-cPr.sub.2 0 0 3736 Cl H SO.sub.2
(Ph-4-OMe) 2-cPr, 3,5-Me.sub.2 0 0 3737 Cl H SO.sub.2 (Ph-4-OMe)
2-cPr, 3,6-Me.sub.2 0 0 3738 Cl H SO.sub.2 (Ph-2-SO.sub.2OQ.sup.6)
2-Me 0 0 3739 Cl H SO.sub.2 (Ph-2-SO.sub.2OQ.sup.7) 2-iPr 0 0 3740
Cl H SO.sub.2 (Ph-2-SO.sub.2OQ.sup.8) 2-cPr 0 0 3741 Cl H
SO.sub.2
(Ph-2-SO.sub.2OQ.sup.9) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3742 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.10) 2,6-Me.sub.2 0 0 3743 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.11) 2-Me, 6-cPr 0 0 3744 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.12) 2-Me, 6-cPr 0 0 3745 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.13) 2-Me, 6-cPr 0 0 3746 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.14) 2-Me, 6-cPr 0 0 3747 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.15) 2-Me, 6-cPr 0 0 3748 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.16) 2-Me, 6-cPr 0 0 3749 Cl H
SO.sub.2 (Ph-2-SO.sub.2OQ.sup.17) 2-Me, 6-cPr 0 0 3750 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.6) 2-Me 0 0 3751 Cl H SO.sub.2
(Ph-3-SO.sub.2OQ.sup.7) 2-iPr 0 0 3752 Cl H SO.sub.2
(Ph-3-SO.sub.2OQ.sup.8) 2-cPr 0 0 3753 Cl H SO.sub.2
(Ph-3-SO.sub.2OQ.sup.9) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3754 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.10) 2,6-Me.sub.2 0 0 3755 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.11) 2-Me, 6-cPr 0 0 3756 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.12) 2-Me, 6-cPr 0 0 3757 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.13) 2-Me, 6-cPr 0 0 3758 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.14) 2-Me, 6-cPr 0 0 3759 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.15) 2-Me, 6-cPr 0 0 3760 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.16) 2-Me, 6-cPr 0 0 3761 Cl H
SO.sub.2 (Ph-3-SO.sub.2OQ.sup.17) 2-Me, 6-cPr 0 0 3762 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.5) 2-Cl, 6-cPr 0 0 3763 Cl H SO.sub.2
(Ph-4-SO.sub.2OQ.sup.6) 2-Me 0 0 3764 Cl H SO.sub.2
(Ph-4-SO.sub.2OQ.sup.7) 2-iPr 0 0 3765 Cl H SO.sub.2
(Ph-4-SO.sub.2OQ.sup.8) 2-cPr 0 0 3766 Cl H SO.sub.2
(Ph-4-SO.sub.2OQ.sup.9) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3767 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.10) 2,6-Me.sub.2 0 0 3768 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.11) 2-Me, 6-cPr 0 0 3769 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.12) 2-Me, 6-cPr 0 0 3770 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.13) 2-Me, 6-cPr 0 0 3771 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.14) 2-Me, 6-cPr 0 0 3772 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.15) 2-Me, 6-cPr 0 0 3773 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.16) 2-Me, 6-cPr 0 0 3774 Cl H
SO.sub.2 (Ph-4-SO.sub.2OQ.sup.17) 2-Me, 6-cPr 0 0 3775 Cl H
SO.sub.2 (Ph-2,5-Cl.sub.2) 2-Me 0 0 3776 Cl H SO.sub.2
(Ph-2,5-Cl.sub.2) 2-iPr 0 0 3777 Cl H SO.sub.2 (Ph-2,5-Cl.sub.2)
2-cPr 0 0 3778 Cl H SO.sub.2 (Ph-2,5-Cl.sub.2)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3779 Cl H SO.sub.2
(Ph-2,5-Cl.sub.2) 2,6-Me.sub.2 0 0 3780 Cl H SO.sub.2
(Ph-2,5-Cl.sub.2) 2-Me, 6-cPr 0 0 3781 Cl H SO.sub.2
(Ph-3-NO.sub.2-4-Cl) 2-Me 0 0 3782 Cl H SO.sub.2
(Ph-3-NO.sub.2-4-Cl) 2-iPr 0 0 3783 Cl H SO.sub.2
(Ph-3-NO.sub.2-4-Cl) 2-cPr 0 0 3784 Cl H SO.sub.2
(Ph-3-NO.sub.2-4-Cl) 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3785 Cl H
SO.sub.2 (Ph-3-NO.sub.2-4-Cl) 2,6-Me.sub.2 0 0 3786 Cl H SO.sub.2
(Ph-3-NO.sub.2-4-Cl) 2-Me, 6-cPr 0 0 3787 Cl H SO.sub.2 (2-Thi)
2-Me 0 0 3788 Cl H SO.sub.2 (2-Thi) 2-iPr 0 0 3789 Cl H SO.sub.2
(2-Thi) 2-cPr 0 0 3790 Cl H SO.sub.2 (2-Thi)
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3791 Cl H SO.sub.2 (2-Thi)
2,6-Me.sub.2 0 0 3792 Cl H SO.sub.2 (2-Thi) 2-Me, 6-cPr 0 0 3793 Cl
H N(Bu).sub.4 2-Me 0 0 3794 Cl H N(Bu).sub.4 2-iPr 0 0 3795 Cl H
N(Bu).sub.4 2-cPr 0 0 3796 Cl H N(Bu).sub.4
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3797 Cl H N(Bu).sub.4 2,6-Me.sub.2
0 0 3798 Cl H N(Bu).sub.4 2-Me, 6-cPr 0 0 3799 Cl H Li 2-Me, 6-cPr
0 0 3800 Cl H Na 2-Me 0 0 3801 Cl H Na 2-iPr 0 0 3802 Cl H Na 2-cPr
0 0 3803 Cl H Na 2CH.sub.2CH.sub.2CH.sub.2-3 0 0 3804 Cl H Na
2,6-Me.sub.2 0 0 3805 Cl H Na 2-Me, 6-cPr 0 0 3806 Cl H K 2-Me 0 0
3807 Cl H K 2-iPr 0 0 3808 Cl H K 2-cPr 0 0 3809 Cl H K
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3810 Cl H K 2,6-Me.sub.2 0 0 3811
Cl H K 2-Me, 6-cPr 0 0 3812 Cl H Rb 2-Me, 6-cPr 0 0 3813 Cl H Cs
2-Me, 6-cPr 0 0 3814 Cl H Mg 2-Me, 6-cPr 0 0 3815 Cl H Ca 2-Me,
6-cPr 0 0 3816 Cl H Ba 2-Me, 6-cPr 0 0 3817 Cl H Sc 2-Me, 6-cPr 0 0
3818 Cl H Ti 2-Me, 6-cPr 0 0 3819 Cl H Mn 2-Me, 6-cPr 0 0 3820 Cl H
Fe 2-Me, 6-cPr 0 0 3821 Cl H Cu 2-Me, 6-cPr 0 0 3822 Cl H Ag 2-Me,
6-cPr 0 0 3823 Cl H Au 2-Me, 6-cPr 0 0 3824 Cl H Zn 2-Me, 6-cPr 0 0
3825 Cl H Al 2-Me, 6-cPr 0 0 3826 Cl F H 2-Me 0 0 3827 Cl F H 2-iPr
0 0 3828 Cl F H 2-cPr 0 0 3829 Cl F H 2-CH.sub.2CH.sub.2CH.sub.2-3
0 0 3830 Cl F H 2,6-Me.sub.2 0 0 3831 Cl F H 2-Me, 6-cPr 0 0 3832
Cl Cl H 2-Me 0 0 3833 Cl Cl H 2-iPr 0 0 3834 Cl Cl H 2-cPr 0 0 3835
Cl Cl H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3836 Cl Cl H 2,6-Me.sub.2
0 0 3837 Cl Cl H 2-Me, 6-cPr 0 0 3838 Cl Br H 2-Me 0 0 3839 Cl Br H
2-iPr 0 0 3840 Cl Br H 2-cPr 0 0 3841 Cl Br H
2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3842 Cl Br H 2,6-Me.sub.2 0 0 3843
Cl Br H 2-Me, 6-cPr 0 0 3844 Cl I H 2-Me 0 0 3845 Cl I H 2-iPr 0 0
3846 Cl I H 2-cPr 0 0 3847 Cl I H 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0
3848 Cl I H 2,6-Me.sub.2 0 0 3849 Cl I H 2-Me, 6-cPr 0 0 3850 Cl H
OCOPh 2-Me, 4-OCOPh 0 0 3851 Cl H CO-4-Thpy 2-Me 0 0 3852 Cl H
CO-4-Thpy 2-iPr 0 0 3853 Cl H CO-4-Thpy 2-cPr 0 0 3854 Cl H
CO-4-Thpy 2-CH.sub.2CH.sub.2CH.sub.2-3 0 0 3855 Cl H CO-4-Thpy
2,6-Me.sub.2 0 0 3856 Cl H CO-4-Thpy 2-Me, 6-cPr 0 0
Among the above-mentioned exemplary compounds, preferred compounds
are Compounds Nos. 124, 125, 126, 127, 128, 130, 131, 132, 134,
136, 139, 140, 144, 145, 151, 163, 173, 202, 207, 217, 226, 249,
264, 265, 266, 267, 269, 270, 271, 272, 273, 279, 280, 284, 287,
292, 300, 304, 305, 306, 307, 308, 309, 311, 330, 334, 336, 339,
344, 359, 361, 362, 364, 365, 370, 377, 385, 386, 387, 390, 391,
400, 401, 403, 410, 412, 413, 417, 422, 426, 437, 438, 441, 443,
446, 450, 456, 459, 472, 478, 498, 505, 506, 507, 514, 515, 516,
521, 527, 528, 529, 531, 532, 534, 535, 539, 541, 544, 547, 557,
562, 566, 571, 614, 618, 621, 623, 629, 640, 642, 658, 659, 662,
663, 664, 667, 700, 701, 702, 704, 707, 708, 710, 711, 712, 716,
717, 719, 728, 732, 733, 734, 735, 736, 737, 738, 740, 756, 758,
759, 760, 761, 762, 775, 778, 780, 781, 782, 801, 802, 803, 804,
805, 806, 827, 834, 844, 845, 846, 850, 890, 894, 896, 911, 914,
931, 964, 965, 979, 982, 987, 998, 1000, 1007, 1009, 1013, 1016,
1020, 1023, 1027, 1040, 1050, 1052, 1053, 1055, 1058, 1060, 1061,
1063, 1064, 1066, 1069, 1073, 1083, 1086, 1088, 1089, 1091, 1096,
1099, 1100, 1102, 1109, 1115, 1118, 1119, 1120, 1122, 1123, 1124,
1125, 1126, 1128, 1129, 1133, 1140, 1151, 1160, 1172, 1178, 1184,
1207, 1251, 1260, 1266, 1286, 1298, 1334, 1340, 1358, 1364, 1382,
1387, 1391, 1417, 1441, 1446, 1448, 1456, 1459, 1461, 1481, 1509,
1522, 1531, 1537, 1543, 1549, 1553, 1554, 1566, 1575, 1593, 1599,
1603, 1616, 1620, 1625, 1631, 1643, 1649, 1658, 1706, 1710, 1757,
1770, 1789, 1811, 1840, 1877, 1879, 1891, 1898, 1911, 1920, 1924,
1937, 1946, 1952, 1958, 1981, 1985, 2010, 2034, 2038, 2040, 2042,
2051, 2060, 2066, 2072, 2081, 2106, 2136, 2147, 2151, 2176, 2198,
2199, 2200, 2212, 2220, 2221, 2222, 2224, 2225, 2263, 2265, 2287,
2289, 2300, 2309, 2315, 2321, 2327, 2333, 2411, 2431, 2453, 2519,
2529, 2540, 2542, 2547, 2548, 2551, 2555, 2556, 2565, 2568, 2570,
2571, 2572, 2574, 2576, 2577, 2585, 2587, 2589, 2592, 2596, 2597,
2599, 2600, 2601, 2603, 2605, 2606, 2607, 2608, 2609, 2614, 2662,
2671, 2677, 2697, 2703, 2709, 2715, 2721, 2727, 2733, 2739, 2746,
2752, 2758, 2764, 2770, 2776, 2782, 2788, 2805, 2814, 2820, 2826,
2827, 2838, 2850, 2856, 2862, 2868, 2874, 2880, 2900, 2906, 2918,
2924, 2930, 2961, 2970, 2976, 2982, 2988, 2994, 3001, 3016, 3022,
3028, 3034, 3040, 3046, 3052, 3058, 3064, 3070, 3076, 3082, 3088,
3094, 3100, 3106, 3112, 3129, 3138, 3144, 3150, 3156, 3162, 3168,
3185, 3194, 3200, 3217, 3226, 3243, 3252, 3258, 3264, 3270, 3276,
3282, 3288, 3294, 3300, 3306, 3312, 3318, 3324, 3330, 3336, 3342,
3348, 3354, 3360, 3366, 3372, 3378, 3384, 3390, 3396, 3402, 3408,
3414, 3420, 3426, 3432, 3438, 3444, 3450, 3456, 3462, 3468, 3474,
3480, 3486, 3492, 3498, 3504, 3510, 3516, 3522, 3528, 3534, 3540,
3546, 3552, 3558, 3564, 3570, 3576, 3582, 3588, 3594, 3600, 3606,
3612, 3618, 3624, 3630, 3636, 3642, 3648, 3654, 3660, 3666, 3672,
3678, 3684, 3690, 3696, 3702, 3708, 3714, 3720, 3755, 3780, 3786,
3792, 3798, 3805, 3811, 3837, 3843 or 3849,
more preferably compounds of Compounds Nos. 124, 125, 126, 127,
128, 130, 132, 136, 139, 140, 144, 145, 151, 163, 173, 202, 217,
249, 264, 265, 266, 267, 269, 270, 271, 284, 287, 300, 304, 308,
309, 311, 334, 336, 339, 361, 362, 377, 385, 386, 387, 390, 391,
401, 437, 438, 459, 472, 505, 506, 507, 515, 516, 521, 528, 529,
531, 532, 534, 539, 541, 544, 547, 571, 621, 658, 659, 662, 663,
664, 667, 700, 701, 702, 704, 707, 708, 711, 712, 717, 719, 732,
733, 734, 735, 736, 737, 738, 740, 756, 758, 759, 760, 762, 775,
778, 780, 781, 782, 801, 802, 803, 806, 827, 834, 845, 846, 850,
896, 914, 931, 964, 965, 998, 1013, 1016, 1023, 1040, 1050, 1052,
1053, 1055, 1058, 1060, 1061, 1063, 1064, 1066, 1069, 1073, 1086,
1088, 1089, 1091, 1096, 1099, 1100, 1102, 1109, 1115, 1118, 1119,
1120, 1123, 1124, 1125, 1126, 1129, 1133, 1140, 1151, 1160, 1172,
1178, 1184, 1207, 1260, 1266, 1286, 1298, 1334, 1340, 1358, 1364,
1382, 1387, 1391, 1417, 1441, 1446, 1448, 1481, 1522, 1531, 1537,
1543, 1549, 1566, 1575, 1593, 1599, 1616, 1620, 1625, 1631, 1643,
1649, 1658, 1710, 1770, 1789, 1811, 1840, 1879, 1891, 1911, 1937,
1946, 1958, 1981, 1985, 2010, 2034, 2038, 2040, 2042, 2051, 2060,
2066, 2072, 2081, 2106, 2136, 2151, 2176, 2200, 2212, 2220, 2225,
2265, 2289, 2300, 2309, 2327, 2333, 2411, 2519, 2529, 2540, 2542,
2556, 2565, 2568, 2576, 2577, 2587, 2597, 2599, 2600, 2601, 2605,
2609, 2614, 2662, 2671, 2677, 2697, 2703, 2709, 2715, 2721, 2727,
2733, 2739, 2746, 2752, 2758, 2764, 2770, 2776, 2782, 2788, 2805,
2814, 2820, 2826, 2850, 2856, 2862, 2868, 2874, 2880, 2900, 2906,
2918, 2924, 2930, 2961, 2970, 2976, 2982, 2988, 2994, 3022, 3028,
3034, 3040, 3046, 3052, 3058, 3064, 3070, 3076, 3082, 3088, 3094,
3100, 3106, 3112, 3129, 3138, 3144, 3162, 3168, 3185, 3194, 3200,
3217, 3226, 3243, 3252, 3258, 3264, 3270, 3276, 3282, 3288, 3294,
3300, 3306, 3312, 3318, 3324, 3330, 3336, 3342, 3348, 3354, 3360,
3366, 3372, 3378, 3384, 3390, 3396, 3402, 3408, 3414, 3420, 3426,
3432, 3438, 3444, 3450, 3456, 3462, 3468, 3474, 3480, 3486, 3492,
3498, 3504, 3510, 3516, 3528, 3534, 3540, 3546, 3552, 3558, 3564,
3570, 3576, 3582, 3588, 3594, 3600, 3606, 3612, 3618, 3624, 3630,
3636, 3642, 3648, 3654, 3660, 3666, 3672, 3678, 3684, 3690, 3696,
3702, 3708, 3714, 3720, 3755, 3780, 3786, 3792, 3798, 3805, 3811,
3837, 3843 or 3849,
still further preferably compounds of Compounds Nos. 125, 126, 127,
128, 130, 132, 139, 140, 144, 145, 151, 163, 217, 249, 264, 265,
266, 284, 304, 308, 387, 390, 391, 459, 472, 506, 507, 515, 516,
531, 539, 541, 621, 658, 659, 662, 700, 701, 702, 704, 711, 717,
719, 733, 734, 735, 740, 758, 759, 762, 775, 780, 781, 801, 802,
803, 806, 827, 834, 846, 850, 931, 964, 965, 1023, 1040, 1050,
1052, 1053, 1055, 1058, 1061, 1064, 1066, 1069, 1073, 1088, 1089,
1091, 1096, 1099, 1100, 1102, 1109, 1119, 1124, 1125, 1126, 1129,
1133, 1151, 1160, 1172, 1178, 1184, 1207, 1260, 1286, 1298, 1334,
1340, 1358, 1382, 1417, 1441, 1481, 1522, 1531, 1537, 1543, 1549,
1566, 1593, 1599, 1616, 1625, 1631, 1643, 1649, 1770, 1811, 1891,
1958, 2034, 2051, 2060, 2072, 2136, 2176, 2212, 2265, 2309, 2327,
2333, 2519, 2556, 2577, 2587, 2597, 2599, 2600, 2601, 2609, 2614,
2662, 2677, 2697, 2709, 2715, 2721, 2727, 2733, 2739, 2746, 2752,
2758, 2764, 2770, 2776, 2782, 2788, 2805, 2814, 2820, 2826, 2850,
2862, 2868, 2874, 2900, 2918, 2924, 2930, 2961, 2970, 2988, 2994,
3022, 3034, 3046, 3058, 3064, 3076, 3082, 3094, 3106, 3112, 3129,
3144, 3162, 3168, 3185, 3217, 3243, 3252, 3264, 3282, 3288, 3294,
3306, 3324, 3330, 3336, 3354, 3378, 3390, 3396, 3402, 3408, 3414,
3420, 3426, 3432, 3438, 3450, 3462, 3468, 3474, 3486, 3492, 3510,
3516, 3546, 3552, 3564, 3582, 3588, 3594, 3600, 3606, 3612, 3618,
3624, 3642, 3654, 3660, 3678, 3690, 3696, 3702, 3780, 3786, 3798,
3805, 3811, 3837, 3843 or 3849,
particularly preferably compounds of Compounds Nos. 127, 128, 132,
139, 144, 217, 265, 284, 304, 391, 472, 506, 507, 515, 516, 539,
541, 621, 658, 659, 662, 704, 711, 717, 719, 733, 735, 740, 758,
759, 762, 780, 781, 801, 802, 803, 806, 827, 846, 850, 931, 964,
965, 1023, 1040, 1052, 1058, 1061, 1088, 1089, 1091, 1096, 1099,
1100, 1102, 1109, 1124, 1125, 1151, 1160, 1172, 1184, 1207, 1286,
1298, 1334, 1358, 1417, 1441, 1481, 1522, 1531, 1537, 1543, 1566,
1593, 1599, 1616, 1625, 1631, 1643, 1770, 1811, 1891, 1958, 2034,
2051, 2176, 2212, 2265, 2309, 2327, 2333, 2597, 2599, 2614, 2662,
2677, 2727, 2733, 2739, 2746, 2752, 2805, 2814, 2850, 2900, 2918,
2961, 2994, 3022, 3046, 3064, 3094, 3129, 3144, 3168, 3185, 3217,
3243, 3264, 3288, 3402, 3408, 3426, 3432, 3450, 3462, 3546, 3552,
3564, 3582, 3588, 3594, 3600, 3606, 3612, 3618, 3624, 3642, 3654,
3660, 3678, 3690, 3696, 3702, 3805 or 3811,
most preferably compounds of
6-chloro-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 128),
6-chloro-3-(2-isopropylphenoxy)-4-pyridazinol (Compound No. 132),
6-chloro-3-(2-cyclopropylphenoxy)-4-pyridazinol (Compound No. 139),
6-chloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 265),
6-chloro-3-(2,3-dihydro-1H-inden-4-yloxy)-4-pyridazinol (Compound
No. 506), 6-chloro-3-(2-cyclopropyl-5-methylphenoxy)-4-pyridazinol
(Compound No. 662),
6-chloro-3-(2-fluoro-6-isopropylphenoxy)-4-pyridazinol (Compound
No. 717), 6-chloro-3-(2-chloro-6-cyclopropylphenoxy)-4-pyridazinol
(Compound No. 740), 6-chloro-3-(2,6-dimethylphenoxy)-4-pyridazinol
(Compound No. 801),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (Compound
No. 806),
6-chloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]-4-pyridazi-
nol (Compound No. 827),
6-chloro-3-(2-cyclopropyl-3,5-dimethylphenoxy)-4-pyridazinol
(Compound No. 1023),
6-chloro-3-(6-cyclopropyl-3-fluoro-2-methylphenoxy)-4-pyridazinol
(Compound No. 1052),
6-chloro-3-(6-cyclopropyl-2,3-dimethylphenoxy)-4-pyridazinol
(Compound No. 1061),
6-chloro-3-(2,3,5,6-tetramethylphenoxy)-4-pyridazinol (Compound No.
1125), 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
acetate (Compound No. 1151),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl propionate
(Compound No. 1160),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-methylpropanoate (Compound No. 1172),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl pivalate
(Compound No. 1207),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-methyl-2-butenoate (Compound No. 1358),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl benzoate
(Compound No. 1417),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-methylbenzoate (Compound No. 1481),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-methoxybenzoate (Compound No. 1522),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-methylbenzoate (Compound No. 1531),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-bromobenzoate (Compound No. 1543),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methylbenzoate (Compound No. 1566),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl phthalate
(Compound No. 1625),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl isophthalate
(Compound No. 1631),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
isobutylcarbonate (Compound No. 1770),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
dimethylcarbamate (Compound No. 1891),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-propanesulfonate (Compound No. 2051),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl benzene
sulfonate (Compound No. 2176),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-chlorobenzene sulfonate (Compound No. 2212),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methylbenzene sulfonate (Compound No. 2265),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methoxybenzene sulfonate (Compound No. 2309),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazoyl-5-yl 1,2-benzene
disulfonate (Compound No. 2327),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl 1,3-benzene
disulfonate (Compound No. 2333),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,3-dimethylbutanoate (Compound No. 2662),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl ethyl
succinate (Compound No. 2727),
bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
succinate (Compound No. 2733),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl pentanedioate
(Compound No. 2739),
bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
pentanedioate (Compound No. 2746),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-bromobenzoate (Compound No. 2805),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-ethylbenzoate (Compound No. 2961),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,5-dimethylbenzoate (Compound No. 3129),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-fluoro-4-methylbenzoate (Compound No. 3185),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,5-difluorobenzoate (Compound No. 3217),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,5-dimethylbenzoate (Compound No. 3243),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
methoxy(methyl)carbamate (Compound No. 3564),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
bis(2-methoxyethyl)carbamate (Compound No. 3600),
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-azetizincarboxylate (Compound No. 3612) or
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-morpholinecarboxylate (Compound No. 3690).
The 3-phenoxy-4-pyridazinol compound and its ester derivative of
the present invention can be produced by the methods described in
the following Steps A to N.
##STR00016##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 have the same meanings as defined in the above,
L represents a leaving group, and for example, it may be a halogen
atom, a C.sub.1 to C.sub.6 alkylsulfonyloxy group or a
phenylsulfonyloxy group (the phenylsulfonyloxy group may be
substituted by the same or different 1 to 5 halogen atom(s) or
C.sub.1 to C.sub.6 alkyl group(s).), X repersents a hydrogen atom
or an acyl group, Y represents, in addition to X, other protective
groups for the hydroxyl group, and for example, it may be a methyl
group, a methoxymethyl group, a methoxyethoxymethyl group or a
benzyl group.
Step A is a step to produce Compound (Ia) of the present invention
or a compound represented by the formula (VII), in which a hydroxyl
group is protected, by reacting a phenol compound represented by
the formula (III) with a pyridazine compound represented by the
formula (II), then, chlorinating the resulting compound, and futher
reacting an oxygen nucleophilic agent, and further a step to
produce Compound (Ib) of the present invention by removing the
protective group of Compound (VII).
(Step A-1)
Step A-1 is a step to produce a phenoxypyridazine compound
represented by the formula (IV) by reacting Compound (II) with
Compound (III) in the presence or absence of a solvent, and if
necessary, in the presence of a base.
The base to be used is not specifically limited so long as it is a
base showing generally a pH of 8 or more, and for example, it may
be alkali metal hydroxides such as sodium hydroxide, potassium
hydroxide, etc.; alkali metal carbonates such as sodium carbonate,
potassium carbonate, cesium carbonate, etc.; metal alkoxides such
as sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.;
alkali metal hydrides such as sodium hydride, potassium hydride,
etc.; alkali metals such as sodium, potassium, etc.; aliphatic
tertiary amines such as triethylamine, tributylamine,
diisopropylethylamine, etc.; aliphatic cyclic tertiary amines such
as 1,4-diazabicyclo[2.2.2]-octane (DABCO),
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc.; pyridines such as
pyridine, collidine, 4-(N,N-dimethylamino)pyridine, etc.; organic
metal bases such as n-butyl lithiums, s-butyl lithium, lithium
diisopropylamide, sodium bis(trimehylsilyl)amide, lithium
bis(trimethylsilyl)amide, etc., preferably alkali metal hydroxides,
alkali metal carbonates, metal alkoxides, alkali metal hydrides or
alkali metals, more preferably potassium carbonate, potassium
t-butoxide, sodium hydride or sodium.
An amount of the base to be used is generally 0.5 to 5 mol,
preferably 1 to 3 mol based on 1 mol of the compound (II).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be water; alcohols
such as methanol, ethanol, t-butanol, etc.; ketones such as
acetone, methyl isobutyl ketone, etc.; nitriles such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; or a mixed
solvent of the above, preferably nitriles, halogenated
hdyrocarbons, ethers, aromatic hydrocarbons, amides or sulfoxides,
more preferably dioxane, toluene, dimethylformamide or
dimethylsulfoxide.
The reaction temperature may vary depending on the starting
compounds, reaction reagents and solvent, etc., and is generally
-90.degree. C. to 200.degree. C., preferably 0.degree. C. to
100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 48 hours,
preferably 15 minutes to 12 hours.
(Step A-2)
Step A-2 is a step to producing a compound represented by the
formula (V) in which a chlorine atom is introduced into the
4-position of a pyridazine ring by chlorinating Compound (IV) with
a chlorinating agent in the presence or absence of a solvent.
As the chlorinating agent to be used, it is not specifically
limited so long as it can chlorinate an aromatic ring, and for
example, it may be chlorine, chlorine-iron chloride, sulfuryl
chloride, copper chloride, N-chlorosuccinimide or phosphorus
pentachloride, preferably chlorine.
An amount of the chlorinating agent to be used is generally 0.5 to
10 mol, preferably 1 to 2 mol based on 1 mol of the compound
(IV).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be phosphorus
oxychloride; water; alcohols such as methanol, ethanol, t-butanol,
etc.; halogenated hydrocarbons such as methylene chloride,
chloroform, dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; aliphatic
hydrocarbons such as hexane, cyclohexane, heptane, etc.; or a mixed
solvent of the above, preferably phosphorus oxychloride, water,
halogenated hdyrocarbons or ethers, more preferably phosphorus
oxychloride.
The reaction temperature may vary depending on the starting
compounds, reaction reagents and a kind of the solvent to be used,
etc., and is generally -90.degree. C. to 200.degree. C., preferably
0.degree. C. to 50.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 24 hours,
preferably 15 minutes to 6 hours.
(Step A-3)
Step A-3 is a step to produce Compound (Ia) of the present
invention or a compound represented by the formula (VII), in which
a hydroxyl group is protected, by reacting Compound (V) with an
oxygen nucleophilic agent represented by the formula (VI) in the
presence or absence of a solvent, and if necessary, in the presence
of a base.
The base to be used is not specifically limited so long as it is a
base showing generally a pH of 8 or more, and for example, it may
be alkali metal hydroxides such as sodium hydroxide, potassium
hydroxide, etc.; alkali metal carbonates such as sodium carbonate,
potassium carbonate, cesium carbonate, etc.; metal alkoxides such
as sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.;
alkali metal salts of an organic acid such as sodium acetate,
potassium acetate, sodium formate, potassium formate, etc.; alkali
metal hydrides such as sodium hydride, potassium hydride, etc.;
alkali metals such as sodium, potassium, etc.; aliphatic tertiary
amines such as triethylamine, tributylamine, diisopropylethylamine,
etc.; aliphatic cyclic tertiary amines such as
1,4-diazabicyclo-[2.2.2]octane (DABCO),
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc.; pyridines such as
pyridine, collidine, 4-(N,N-dimethylamino)pyridine, etc.; organic
metal bases such as n-butyl lithiums, s-butyl lithium, lithium
diisopropylamide, sodium bis(trimehylsilyl)amide, lithium
bis(trimethylsilyl)amide, etc., preferably alkali metal hydroxides,
alkali metal carbonates, metal alkoxide, alkali metal salts of an
organic acid, alkali metal hydrides or alkali metals, more
preferably sodium hydroxide, potassium hydroxide, potassium
carbonate, potassium t-butoxide, sodium acetate, sodium formate,
sodium hydride or sodium.
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, for example, water; alcohols such as
methanol, ethanol, t-butanol, etc.; ketones such as acetone, methyl
isobutyl ketone, etc.; nitriles such as acetonitrile, etc.; esters
such as ethyl acetate, etc.; halogenated hydrocarbons such as
methylene chloride, chloroform, dichloroethane, etc.; ethers such
as diethyl ether, tetrahydrofuran, dioxane, etc.; aromatic
hydrocarbons such as toluene, etc.; amides such as
dimethylformamide, dimethylacetamide, etc.; sulfoxides such as
dimethylsulfoxide, etc.; or a mixed solvent of the above,
preferably water, alcohols, nitriles, ethers, amides or sulfoxides,
more preferably water, methanol, acetonitrile, tetrahydrofuran,
dioxane, dimethylformamide or dimethylsulfoxide.
The reaction temperature may vary depending on the starting
compounds, reaction reagents and a kind of the solvent to be used,
etc., and is generally -90.degree. C. to 200.degree. C., preferably
0.degree. C. to 100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and is usually 5 minutes to 24 hours,
preferably 15 minutes to 6 hours.
Incidentally, in the present step, the compound (VI) may be used in
the present step after making a salt by previously reacting with a
base.
(Step A-4)
Step A-4 is a step to produce Compound (Ib) of the present
invention by removing the protective group for a hydroxyl group of
Compound (VII).
The protective group to be used in the present step is not
specifically limited so long as it can selectively removed from
Compound (VII) to provide Compound (Ib), and for example, it may be
a methyl group, methoxymethyl group, benzyloxymethyl group,
methoxyethoxymethyl group, 2-(trimethylsilyl)ethoxymethyl group,
methylthiomethyl group, phenylthiomethyl group,
2,2-dichloro-1,1-difluoroethyl group, tetrahydropyranyl group,
phenacyl group, p-bromophenacyl group, cyclopropylmethyl group,
allyl group, isopropyl group, cyclohexyl group, t-butyl group,
benzyl group, 2,6-dimethylbenzyl group, 4-methoxybenzyl group,
2-nitrobenzyl group, 2,6-dichlorobenzyl group,
4-(dimethylaminocarbonyl)benzyl group, 9-anthrylmethyl group,
4-picolyl group, heptafluoro-p-tolyl group or tetrafluoro-4-pyridyl
group, preferably a methyl group, methoxymethyl group,
methoxyethoxymethyl group, methylthiomethyl group,
tetrahydropyranyl group, phenacyl group, allyl group or benzyl
group, more preferably a methyl group.
A method for removing the protective group to be used in the
present step is not specifically limited so long as it can
selectively remove the protective group for a hydroxyl group, and
it can be carried out by the conventionally known method (for
example, a method described in Protective Groups in Organic
Synthesis, 13.sup.th Edition, written by Theodora W. Greene and
Peter G. M. Wuts, JOHN WILEY & SONS, INC.) with regard to the
respective protecttive groups or in accordance with these methods.
For example, when the protective group is a methyl group, removal
of the methyl group can be carried out, for example, by reacting
with a potassium salt or sodium salt of 2-hydroxypyridine in
dimethylsulfoxide, a sodium salt of ethanethiol in
dimethylformamide, or boron tribromide in methylene chloride. For
example, when the protective group is a methoxymethyl group,
removal of the methoxymethyl group can be carried out, for example,
by reacting with trifluoroacetic acid. For example, when the
protective group is a methoxyethoxymethyl group, removal of the
methoxyethoxymethyl group can be carried out, for example, by
reacting with trifluoroacetic acid. Also, for example, when the
protective group is a benzyl group, removal of the benzyl group can
be carried out by catalytic hydrogenation.
##STR00017##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7, L, X and Y have the same meanings as defined in
the above.
Step B is a step to produce Compound (Ia) of the present invention
or a compound represented by the formula (VII), in which a hydroxyl
group is protected, by oxidizing a pyridazine compound represented
by the formula (II), reacting a phenol compound represented by the
formula (III) to the resulting compound, then chlorinating the
resulting compound, and further reacting an oxygen nucleophilic
agent, or a step to produce Compound (Ib) of the present invention
by removing the protective group of Compound (VII).
(Step B-1)
Step B-1 is a step to produce Pyridazine N-oxide represented by the
formula (VIII) by oxidizing Compound (II) with an oxidizing agent
in the presence or absence of a solvent.
The oxidizing agent to be used is not specifically limited so long
as it can convert an amine into an N-oxide, and for example, it may
be peroxides such as m-chloroperbenzoic acid (mcpba), peracetic
acid, pertrifluoroacetic acid, trifluoroacetic anhydride-hydrogen
peroxide, peroxydichloromaleic acid, dichloromaleic acid-hydrogen
peroxide, peroxymaleic acid, maleic acid-hydrogen peroxide,
t-butylhydroperoxide, t-butylhydroperoxide-vanadium
oxyacetylacetonate, t-butylhydroperoxide-molybdenum chloride,
hydrogen peroxide, etc.; ozone; or oxygen, preferably
m-chloroperbenzoic acid (mcpba), trifluoroacetic anhydride-hydrogen
peroxide or dichloromaleic acid-hydrogen peroxide.
An amount of the oxidizing agent to be used in the reaction is
usually 0.5 to 100 mol, preferably 1 to 2 mol based on 1 mol of
Compound (II).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be water; alcohols
such as methanol, ethanol, t-butanol, etc.; ketones such as
acetone, methyl isobutyl ketone, etc.; nitriles such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; or a mixed
solvent of the above, preferably halogenated hdyrocarbons, more
preferably methylene chloride.
The reaction temperature may vary depending on the starting
compounds, reaction reagents and solvents, etc., and is generally
-90.degree. C. to 200.degree. C., preferably 0.degree. C. to
100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 24 hours,
preferably 15 minutes to 6 hours.
According to the present step, an isomer in which other nitrogen
atom is oxidized may be by-produced in some cases, and an objective
Pyridazine N-oxide can be obtained by purifying the resulting
materials after completion of the present step, or carrying out the
subsequent steps in a state of admixture and by purifying the
resulting materials after completion of the step.
(Step B-2)
Step B-2 is a step to produce a phenoxypyridazine compound
represented by the formula (IX) by reacting Compound (VIII) with
Compound (III) in the presence or absence of a solvent, and if
necessary, in the presence of a base.
The present step can be carried out in accordance with Step
A-1.
(Step B-3)
Step B-3 is a step to produce Compound (V) by reacting Compound
(IX) with phosphorus oxychloride in the presence or absence of a
solvent.
An amount of the phosphorus oxychloride to be used in the present
step is generally 0.5 to 100 mol, preferably 1 to 5 mol based on 1
mol of Compound (IX).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be ketones such as
acetone, methyl isobutyl ketone, etc.; nitriles such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; aliphatic
hydrocarbons such as hexane, cyclohexane, etc.; or a mixed solvent
of the above, preferably halogenated hdyrocarbons, more preferably
methylene chloride or chloroform.
The reaction temperature may vary depending on the starting
compounds, reaction reagents and solvents, etc., and is generally
-90.degree. C. to 200.degree. C., preferably 0.degree. C. to
100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 72 hours,
preferably 30 minutes to 24 hours.
(Step B-4)
Step B-4 is a step to produce Compound (Ia) of the present
invention or a compound represented by the formula (VII), in which
a hydroxyl group is protected, by reacting Compound (V) with an
oxygen nucleophilic agent represented by the formula (VI) in the
presence or absence of a solvent, and if necessary, in the presence
of a base.
The present step is similar to Step A-3.
(Step B-5)
Step B-5 is a step to produce Compound (Ib) of the present
invention by removing the protective group for a hydroxyl group of
Compound (VII).
The present step is similar to Step A-4.
##STR00018##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7, X and Y have the same meanings as defined in the
above.
Step C is a step to produce Compound (Ia) of the present invention
or a compound represented by the formula (VII), in which a hydroxyl
group is protected, by oxidizing Compound (IV), then chlorinating
the resulting material, and then reacting the same with an oxygen
nucleophilic agent, and further a step to produce Compound (Ib) of
the present invention by removing the protective group of Compound
(VII).
(Step C-1)
Step C-1 is a step to produce Pyridazine N-oxide represented by the
formula (IX) by oxidizing Compound (IV) with an oxidizing agent in
the presence or absence of a solvent.
The present step can be carried out in accordance with Step
B-1.
(Step C-2)
Step C-2 is a step to produce Compound (V) by reacting Compound
(IX) with phosphorus oxychloride in the presence or absence of a
solvent.
The present step is similar to Step B-3.
(Step C-3)
Step C-3 is a step to produce Compound (Ia) of the present
invention or a compound represented by the formula (VII), in which
a hydroxyl group is protected, by reacting Compound (V) with an
oxygen nucleophilic agent represented by the formula (VI) in the
presence or absence of a solvent, and if necessary, in the presence
of a base.
The present step is similar to Step A-3 or B-4.
(Step C-4)
Step C-4 is a step to produce Compound (Ib) of the present
invention by removing the protective group for a hydroxyl group of
Compound (VII).
The present step is similar to Step A-4 or B-5.
##STR00019##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7, L, X and Y have the same meanings as defined
above.
Step D is a step to produce Compound (Ia) of the present invention
or a compound represented by the formula (VII), in which a hydroxyl
group is protected, by reacting a pyridazine compound represented
by the formula (X), into which an oxygen functional group has
previously been substituted, with a phenol represented by the
formula (III), and further a step to produce Compound (Ib) of the
present invention by removing the protective group of Compound
(VII).
(Step D-1)
Step D-1 is a step to produce Compound (Ia) of the present
invention or a compound represented by the formula (VII), in which
a hydroxyl group is protected, by reacting Compound (X) with
Compound (III) in the presence or absence of a solvent, and if
necessary, in the presence of a base.
The present step can be carried out in accordance with Step A-1 or
B-2.
(Step D-2)
Step D-2 is a step to produce Compound (Ib) of the present
invention by removing the protective group for a hydroxyl group for
Compound (VII).
The present step is similar to Step A-4, B-5 or C-4.
##STR00020##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7, L, X and Y have the same meanings as defined
above, m' and n' each represent 0 or 1, provided that m' and n' are
not simultaneously 0.
Step E is a step to produce Compound (Ic) of the present invention
or a compound represented by the formula (XII), in which a hydroxyl
group is protected, by oxidizing a pyridazine compound to which an
oxygen functional group has previously been substituted represented
by the formula (X), and then reacting a phenol represented by the
formula (III), and further a step to produce Compound (Id) of the
present invention by removing the protective group of Compound
(XII).
(Step E-1)
Step E-1 is a step to produce Pyridazine N-oxide represented by the
formula (XI) by oxidizing Compound (X) with an oxidizing agent in
the presence or absence of a solvent.
The present step can be carried out in accordance with Step B-1 or
C-1 in the case where m'=0 or n'=0, and when m'=n'=1, it can be
carried out under severer conditions by making an amount of the
oxidizing agent in excessive, by using an oxidizing agent having
higher reactivity to carry out the oxidation, and the like.
(Step E-2)
Step E-2 is a step to produce Compound (Ic) of the present
invention or a compound represented by the formula (XII), in which
a hydroxyl group is protected, by reacting Compound (XI) with
Compound (III) in the presence or absence of a solvent, and if
necessary, in the presence of a base.
The present step can be carried out in accordance with Step A-1,
B-2 or D-1.
(Step E-3)
Step E-3 is a step to produce Compound (Id) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XII).
The present step is similar to Step A-4, B-5, C-4 or D-2.
##STR00021##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7, X, Y, m' and n' have the same meanings as defined
above.
Step F is a step to produce Compound (Ic) of the present invention
or a compound represented by the formula (XII), in which a hydroxyl
group is protected, by oxidizing Compound (Ia) of the present
invention or a compound represented by the formula (VII) in which a
hydroxyl group is protected, and further is a step to produce
Compound (Id) of the present invention by removing the protective
group of Compound (XII).
(Step F-1)
Step F-1 is a step to produce Compound (Ic) of the present
invention or a compound represented by the formula (XII), in which
a hydroxyl group is protected, by oxidizing Compound (Ia) of the
present invention or Compound (VII) with an oxidizing agent in the
presence or absence of a solvent.
The present step can be carried out in accordance with Step
E-1.
(Step F-2)
Step F-2 is a step to produce Compound (Id) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XII).
The present step is similar to Step A-4, B-5, C-4, D-2 or E-3.
##STR00022##
In the above formula, R.sup.1, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, X and Y have the same meanings as defined above, R.sup.2a
has the same meaning as R.sup.2 except for removing a hydrogen
atom.
Step G is a step to produce Compound (If) of the present invention
or a compound represented by the formula (XIV), in which a hydroxyl
group is protected, by subjecting the 5-position of the pyridazine
ring of Compound (Ie) of the present invention or a compound
represented by the formula (XIII), in which a hydroxyl group is
protected, to metalation, and then reacting an electrophilic agent
to the resulting material, and further is a step to produce
Compound (Ig) of the present invention by removing the protective
group of Compound (XIV).
(Step G-1)
Step G-1 is a step to produce Compound (If) of the present
invention or a compound represented by the formula (XIV), in which
a hydroxyl group is protected, by reacting Compound (Ie) of the
present invention or a compound represented by the formula (XIII),
in which a hydroxyl group is protected, with a metalating agent in
the presence or absence of a solvent, and then, reacting with an
electrophilic agent.
The metalating agent to be used is not specifically limited so long
as it can metalate an aromatic ring, and for example, it may be
organic lithium compounds such as methyl lithium, butyl lithium,
s-butyl lithium, t-butyl lithium, phenyl lithium, etc.; organic
magnesium compounds such as methylmagnesium chloride, methyl
magnesium bromide, ethyl magnesium bromide, phenylmagnesium
bromide, etc.; organometal amides such as lithium diisopropylamide,
sodium bis(trimethylsilyl)amide, lithium bis(trimethylsilyl)amide,
etc.; metal alkoxides such as sodium methoxide, sodium ethoxide,
potassium t-butoxide, etc.; alkali metal hydrides such as sodium
hydride, potassium hydride, etc.; alkali metals such as lithium,
sodium, potassium, etc.; alkaline earth metals such as magnesium,
etc., preferably organic lithium compounds, more preferably butyl
lithium.
An amount of the metalating agent to be used in the reaction is
generally 0.5 to 10 mol, preferably 1 to 2 mol based on 1 mol of
Compound (Ie) or Compound (XIII).
The electrophilic agent to be used in the reaction is not
specifically limited so long as it can be a nucleophilic agent
capable of reacting with an organometallic compound, and for
example, it may be silylating agents such as trimethylsilyl
chloride, triethylsilyl chloride, t-butyldimethylsilyl chloride,
trimethylsilyl trifluoromethane sulfonate, etc.; acylating agents
such as acetyl chloride, benzoyl chloride, ethyl chlorocarbonate,
methyl chlorocarbonate, N,N-dimethylformamide, methyl formate,
etc.; carbonyl compounds such as acetaldehyde, benzaldehyde,
acetone, cyclohexanone, etc.; alkylating agents such as methyl
iodide, methyl bromide, benzyl bromide, etc.; halogenating agents
such as fluorine, chlorine, bromine, iodine, N-fluorobenzene
sulfonamide, 1-fluoro-2,6-dichloropyridinium triflate,
N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), etc.; or
carbon dioxide, preferably a silylating agent, acylating agent,
alkylating agent or halogenating agent, more preferably
trimethylsilyl chloride, benzoyl chloride, ethyl chlorocarbonate or
methyl iodide.
An amount of the electrophilic agent to be used in the reaction is
generally 0.5 to 10 mol, preferably 1 to 3 mol based on 1 mol of
Compound (Ie) or Compound (XIII).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; aliphatic hydrocarbons such as hexane, cyclohexane,
etc.; or a mixed solvent of the above, preferably ethers, more
preferably tetrahydrofuran.
The reaction temperature may vary depending on starting materials,
reaction reagents and a kind of the solvent to be used, etc., and
usually -90.degree. C. to 100.degree. C., preferably -70.degree. C.
to 30.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 24 hours,
preferably 30 minutes to 12 hours.
(Step G-2)
Step G-2 is a step to produce Compound (Ig) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XIV).
The present step is similar to Step A-4, B-5, C-4, D-2, E-3 or
F-2.
##STR00023##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 have the same meanings as defined above,
X.sup.a represents the same meanings as X except for removing a
hydrogen atom.
Step H is a step to convert an ester derivative represented by the
formula (Ih) of the present invention into a hydroxy compound
represented by the formula (Ib) of the present invention.
(Step H-1)
Step H-1 is a step to produce Compound (Ib) of the present
invention by reacting Compound (Ih) of the present invention with a
nucleophilic agent in the presence or absence of a solvent.
The nucleophilic agent to be used is not specifically limited so
long as it can nucleophilically attack an ester derivative, and
cleave the ester bonding to an acid portion and an alcohol portion,
and for example, it may be water; hydroxides of an alkali metal
such as lithium hydroxide, sodium hydroxide, potassium hydroxide,
etc.; hydroxides of an alkaline earth metal such as magnesium
hydroxide, calcium hydroxide, etc.; metal alkoxides such as sodium
methoxide, sodium ethoxide, 2-hydroxypyridine potassium salt,
2-hydroxypyridine sodium salt, etc.; alkali metal salts of an
organic acid such as sodium acetate, potassium acetate, sodium
formate, potassium formate, etc.; fluorides such as
tetrabutylammonium fluoride, potassium fluoride, etc.; chlorides
such as lithium chloride, sodium chloride, etc.; bromides such as
lithium bromide, sodium bromide, etc.; iodides such as sodium
iodide, potassium iodide, etc.; or metal salts of a sulfur compound
such as methanethiol sodium salt, ethanethiol sodium salt, etc.,
preferably water, hydroxides of an alkali metal, metal alkoxides or
alkali metal salts of an organic acid, more preferably water,
sodium hydroxide, potassium hydroxide or sodium acetate.
An amount of the nucleophilic agent to be used is generally 1 to 10
mol, preferably 1 to 5 mol based on 1 mol of Compound (Ih).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be water; alcohols
such as methanol, ethanol, t-butanol, etc.; ketones such as
acetone, methyl isobutyl ketone, etc.; nitrites such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; or a mixed
solvent of the above, preferably water, alcohols, nitrites, ethers,
amides or sulfoxides, more preferably water, methanol, ethanol,
tetrahydrofuran, dioxane, dimethylformamide or
dimethylsulfoxide.
The reaction temperature may vary depending on starting materials,
reaction reagents and a kind of the solvent to be used, etc., and
usually -90.degree. C. to 200.degree. C., preferably 0.degree. C.
to 100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 48 hours,
preferably 15 minutes to 12 hours.
Incidentally, in the present step, a conventionally known method
can be employed as usual deprotection of a hydroxyl group.
##STR00024##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7 and X.sup.a have the same meanings as defined
above.
Step I is a step to convert the hydroxy compound represented by the
formula (Ib) of the present invention tinot an ester derivative
represented by the formula (Ih) of the present invention.
(Step I-1)
Step I-1 is a step to produce Compound (Ih) of the present
invention by reacting Compound (Ib) of the present invention with
an esterifyng agent in the presence or absence of a solvent.
The esterifying agent to be used is not specifically limited so
long as it can esterify a hydroxyl group, and for example, it may
be acylating agents such as acetyl chloride, acetyl bromide, acetic
anhydride, trifluoroacetic anhydride, benzoyl chloride, methyl
chlorocarbonate, ethyl chlorocarbonate, N,N-dimethylcarbamoyl
chloride, methyl chlorothioformate, etc.; or sulfonylating agents
such as methanesulfonyl chloride, propanesulfonyl chloride,
p-toluenesulfonyl chloride, trifluoromethanesulfonic acid
anhydride, N,N-dimethylsulfamoyl chloride, etc., preferably acetyl
chloride, acetic anhydride, trifluoroacetic anhydride, benzoyl
chloride, methyl chlorocarbonate, ethyl chlorocarbonate,
methanesulfonyl chloride, propanesulfonyl chloride,
p-toluenesulfonyl chloride or trifluoromethanesulfonic acid
anhydride, more preferably benzoyl chloride, p-toluenesulfonyl
chloride or trifluoromethanesulfonic acid anhydride.
An amount of the esterifying agent to be used in the reaction is
generally 0.5 to 10 mols, preferably 1 to 3 mols based on 1 mol of
Compound (Ib).
The reaction is preferably carried out in the presence of a
base.
The base to be used is not specifically limited so long as it is a
base showing a pH of 8 or more, and for example, it may be alkali
metal hydroxides such as sodium hydroxide, potassium hydroxide,
etc.; alkali metal carbonates such as sodium carbonate, potassium
carbonate, cesium carbonate, etc.; metal alkoxides such as sodium
methoxide, sodium ethoxide, potassium t-butoxide, etc.; alkali
metal hydrides such as sodium hydride, potassium hydride, etc.;
aliphatic tertiary amines such as triethylamine, tributylamine,
diisopropylethylamine, etc.; aliphatic cyclic tertiary amines such
as 1,4-diazabicyclo-[2.2.2]octane (DABCO),
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc.; pyridines such as
pyridine, collidine, 4-(N,N-dimethylamino)pyridine, etc.; or
organic metal bases such as n-butyl lithiums, s-butyl lithium,
lithium diisopropylamide, sodium bis(trimehylsilyl)amide, lithium
bis(trimethylsilyl)amide, etc., preferably aliphatic tertiary
amines, aliphatic cyclic tertiary amines or pyridines, more
preferably triethylamine, 1,4-diazabicyclo[2.2.2]octane (DABCO),
pyridine or 4-(N,N-dimethylamino)pyridine.
An amount of the base to be used in the reaction is generally 0.5
to 20 mols, preferably 1 to 5 mols based on 1 mol of Compound
(Ib).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be ketones such as
acetone, methyl isobutyl ketone, etc.; nitrites such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; aliphatic hydrocarbons such as hexane, cyclohexane,
etc.; amides such as dimethylformamide, dimethylacetamide, etc.;
sulfoxides such as dimethylsulfoxide, etc.; or a mixed solvent of
the above, preferably nitriles, halogenated hdyrocarbons or ethers,
more preferably acetonitrile or methylene chloride.
The reaction temperature may vary mainly depending on starting
materials, reaction reagents and a kind of the solvent to be used,
and usually -90.degree. C. to 200.degree. C., preferably 0.degree.
C. to 100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 48 hours,
preferably 15 minutes to 12 hours.
Incidentally, in the present step, a conventionally known method
can be employed as usual protection of a hydroxyl group.
##STR00025##
In the above formula, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, X and Y have the same meanings as defined above, R.sup.1a
represents the same meaning as R.sup.1 except for removing a
hydrogen atom.
Step J is a step to produce Compound (Ii) of the present invention
or a compound represented by the formula (XVIII), in which a
hydroxyl group is protected, by reducing, oxidizing and then
metalating a 6-chloropyridazine derivative represented by the
formula (IVa), and reacting the resulting material with an
electrophilic agent to introduce a substituent on the 6-position of
a pyridazine ring, and further subjecting to chlorination, and
substitution reaction with an oxygen nucleophilic agent, and
further, a step to produce Compound (Ij) of the present invention
by removing the protective group of Compound (XVIII).
(Step J-1)
Step J-1 is a step to produce Compound (IVb) in which R.sup.1 in
Compound (IV) is a hydrogen atom by reacting Compound (IVa) in
which R.sup.1 in Compound (IV) is a chlorine atom with a reducing
agent in the presence or absence of a solvent.
The reducing agent to be used in the reaction is not specifically
limited so long as it can reduce a chlorine atom on an aromatic
ring, and for example, it may be a reducing agent to be used in a
usual hydrogenation reaction, preferably hydrogen-palladium
catalyst.
When the hydrogenation reaction is carried out in the present step,
a hydrogen pressure is generally 1 atm to 100 atms, preferably 1 to
3 atms.
An amount of the palladium to be used in the hydrogenation reaction
is generally 0.001 to 10 mols, preferably 0.01 to 1 mol based on 1
mol of Compound (IVa).
The hydrogenation reaction is preferably carried out in the
presence of a base.
The base to be used is not specifically limited so long as it is a
base showing a pH of generally 8 or more, and for example, alkali
metal hydroxides such as sodium hydroxide, potassium hydroxide,
etc.; alkali metal carbonates such as sodium carbonate, potassium
carbonate, cesium carbonate, etc.; metal alkoxides such as sodium
methoxide, sodium ethoxide, potassium t-butoxide, etc.; alkali
metal hydrides such as sodium hydride, potassium hydride, etc.;
aqueous ammonia; aliphatic tertiary amines such as triethylamine,
tri-n-butylamine, diisopropylethylamine, etc.; aliphatic cyclic
tertiary amines such as 1,4-diazabicyclo[2.2.2]octane (DABCO),
1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU), etc.; pyridines such as
pyridine, collidine, 4-(N,N-dimethylamino)pyridine, etc.; or
organometallic bases such as butyl lithium, s-butyl lithium,
lithium diisopropylamide, sodium bis(trimethylsilyl)amide, lithium
bis(trimethylsilyl)amide, etc., preferably aqueous ammonia or
aliphatic tertiary amines, more preferably aqueous ammonia or
triethylamine.
An amount of the base to be used in the reaction is generally 0.1
to 100 mols, preferably 1 to 3 mols based on 1 mol of Compound
(IVa).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be water; alcohols
such as methanol, ethanol, t-butanol, etc.; ketones such as
acetone, methyl isobutyl ketone, etc.; nitriles such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; aliphatic
hydrocarbons such as hexane, cyclohexane, etc.; or a mixed solvent
of the above, preferably alcohols, more preferably methanol or
ethanol.
The reaction temperature may vary mainly depending on starting
materials, reaction reagents and a kind of the solvent to be used,
and usually -90.degree. C. to 200.degree. C., preferably 0.degree.
C. to 100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 48 hours,
preferably 15 minutes to 12 hours.
(Step J-2)
Step J-2 is a step to produce Pyridazine N-oxide represented by the
formula (XV) by oxidizing Compound (IVb) with an oxidizing agent in
the presence or absence of a solvent.
The present step can be carried out in accordance with Step B-1 or
C-1.
(Step J-3)
Step J-3 is a step to produce Compound (XVI) of the present
invention by reacting Compound (XV) with a metalating agent in the
presence or absence of a solvent, and then, reacting with an
electrophilic agent.
The present step can be carried out in accordance with Step
G-1.
(Step J-4)
Step J-4 is a step to produce Compound (XVII) by reacting Compound
(XVI) with phosphorus oxychloride in the presence or absence of a
solvent.
The present step is similar to Step B-3 or C-2.
(Step J-5)
Step J-5 is a step to produce Compound (Ii) of the present
invention or a compound represented by the formula (XVIII), in
which a hydroxyl group is protected, by reacting Compound (XVII)
with an oxygen nucleophilic agent represented by the formula (VI)
in the presence or absence of a solvent, and if necessary, in the
presence of a base.
The present step is similar to Step A-3, B-4 or C-3.
(Step J-6)
Step J-6 is a step to produce Compound (Ij) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XVIII).
The present step is similar to Step A-4, B-5, C-4, D-2, E-3, F-2 or
G-2.
##STR00026##
In the above formula, R.sup.1a, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6, R.sup.7, X and Y have the same meanings as defined
above.
Step K is a step to produce Compound (Ii) of the present invention
or a compound represented by the formula (XVIII), in which a
hydroxyl group is protected, by oxidizing, dechlorinating and then
metalating 6-chloropyridazine derivative represented by the formula
(Ik) of the present invention or a 6-chloropyridazine derivative
represented by the formula (XIX) in which a hydroxyl group is
protected, then introducing an electrophilic agent and finally
reducing the resulting material, and further a step to produce
Compound (Ij) of the present invention by removing the protective
group of Compound (XVIII).
(Step K-1)
Step K-1 is a step to produce a N-oxypyridazine compound
represented by the formula (Il) or (XX) by oxidizing Compound (Ik)
or Compound (XIX) with an oxidizing agent in the presence or
absence of a solvent.
The present step can be carried out in accordance with Step B-1,
C-1 or J-2.
(Step K-2)
Step K-2 is a step to produce a N-oxide compound (Im) or (XXI), in
which the 6-position of the pyridazine ring is a hydrogen atom, by
reacting a N-oxide compound (Il) or (XX), in which the 6-position
of the pyridazine ring is a chlorine atom, with a reducing agent in
the presence or absence of a solvent.
The present step can be carried out in accordance with Step
J-1.
(Step K-3)
Step K-3 is a step to produce Compound (In) of the present
invention or a compound represented by the formula (XXII), in which
a hydroxyl group is protected, by reacting Compound (Im) or (XXI)
with a metalating agent in the presence or absence of a solvent,
and then, reacting with an electrophilic agent.
The present step can be carried out in accordance with Step G-1 or
J-3.
(Step K-4)
Step K-4 is a step to produce Compound (Ii) of the present
invention or a compound represented by the formula (XVIII), in
which a hydroxyl group is protected, by reacting a N-oxide
derivative represented by the formula (In) or (XXII) with
phosphorus trichloride or phosphorus tribromide in the presence or
absence of a solvent.
An amount of the phosphorus trichloride or phosphorus tribromide to
be used is generally 0.5 to 100 mols, preferably 1 to 20 mols based
on 1 mol of Compound (In) or (XXII).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; aliphatic
hydrocarbons such as hexane, cyclohexane, heptane, etc.; or a mixed
solvent of the above, preferably halogenated hydrocarbons, more
preferably chloroform.
The reaction temperature may vary mainly depending on starting
materials, reaction reagents and a kind of the solvent to be used,
and usually -90.degree. C. to 200.degree. C., preferably 0.degree.
C. to 100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 24 hours,
preferably 15 minutes to 6 hours.
(Step K-5)
Step K-5 is a step to produce Compound (Ij) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XVIII).
The present step is similar to Step A-4, B-5, C-4, D-2, E-3, F-2,
G-2 or J-6.
##STR00027##
In the above formula, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, X and Y have the same meanings as defined above, R.sup.1b
represents the same meaning as R.sup.1 except for removing a
hydrogen atom and a halogen atom.
Step L is a step to produce Compound (Io) or a compound represented
by the formula (XXIII), in which a hydroxyl group is protected, by
reacting a 6-chloropyridazine derivative represented by the formula
(Ik) or (XIX) with an organometallic compound, and further a step
to produce Compound (Ip) of the present invention by removing the
protective group of Compound (XXIII).
(Step L-1)
Step L-1 is a step to produce Compound (Io) of the present
invention or a compound represented by the formula (XXIII), in
which a hydroxyl group is protected, by reacting Compound (Ik) or
(XIX) with an organometallic compound in the presence or absence of
a solvent and in the presence of a metal catalyst.
The organometallic compound to be used is not specifically limited
so long as it is used for a cross-coupling reaction in which a
R.sup.1b group is substituted by a chlorine atom, and for example,
it may be organic magnesium compounds such as methyl magnesium
chloride, ethyl magnesium bromide, phenylmagnesium chloride, etc.;
organic zinc compounds such as phenyl zinc chloride, etc.; organic
aluminum compounds such as (diisobutyl)(1-hexenyl)aluminum, etc.;
organic tin compounds such as (vinyl)trimethyl tin,
(1-ethoxyvinyl)tributyltin, (2-furyl)tributyltin,
(2-thienyl)tributyltin, etc.; organic boron compounds such as
phenylboronic acid, etc.; organic silicate compounds such as
trimethylvinylsilicon-tris(dimethylamino)sulfonium
difluorotrimethyl silicate, etc.; potassium cyanide, and acetylene
compounds such as trimethylsilyl acetylene, phenyl acetylene, etc.
may be used similarly in the presence of amines such as
triethylamine, etc., as in the above-mentioned organometallic
compounds, preferably organic tin compounds or organic boron
compounds.
An amount of the organometallic compound to be used in the reaction
is generally 0.5 to 10 mols, preferably 1 to 2 mols based on 1 mol
of Compound (Ik) or (XIX).
The metal catalyst to be used in the present step is not
specifically limited so long as it can be used in a cross-coupling
reaction, and for example, it may be a nickel catalyst or a
palladium catalyst.
An amount of the metal catalyst to be used in the reaction is
generally 0.0001 to 10 mols, preferably 0.01 to 0.5 mol based on 1
mol of Compound (Ik) or (XIX).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be water; alcohols
such as methanol, ethanol, t-butanol, etc.; ketones such as
acetone, methyl isobutyl ketone, etc.; nitrites such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; aliphatic
hydrocarbons such as hexane, cyclohexane, etc.; organic amines such
as triethylamine, pyridine, etc.; or a mixed solvent of the above,
preferably ethers, aromatic hydrocarbons or amides, more preferably
ether, tetrahydrofuran, toluene or dimethylformamide.
The reaction temperature may vary mainly depending on starting
materials, reaction reagents and a kind of the solvent to be used,
and usually -90.degree. C. to 200.degree. C., preferably 0.degree.
C. to 130.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 48 hours,
preferably 15 minutes to 24 hours.
(Step L-2)
Step L-2 is a step to produce Compound (Ip) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XXIII).
The present step is similar to Step A-4, B-5, C-4, D-2, E-3, F-2,
G-2, J-6 or K-5.
##STR00028##
In the above formula, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, X and Y have the same meanings as defined above.
Step M is a step to produce Compound (Iq) of the present invention
or a compound represented by the formula (XXIV), in which a
hydroxyl group is protected, by cyanation of 6-position
unsubstituted Pyridazine N-oxide derivative represented by the
formula (Im) or (XXI), and also a step to produce Compound (Ir) of
the present invention by removing the protective group of Compound
(XXIV).
(Step M-1)
Step M-1 is a step to produce Compound (Iq) of the present
invention or a compound represented by the formula (XXIV), in which
a hydroxyl group is protected, by reacting Compound (Im) or (XXI)
with a cyanation reagent in the presence or absence of a
solvent.
The present step can be carried out in accordance with the
conventionally known Reissert-Henze reaction (JOC, 48, 1983, 1375
to 1377; Heterocycles, 15, 1981, 981 to 984; Synthesis, 1983, 316
to 319, etc.).
(Step M-2)
Step M-2 is a step to produce Compound (Ir) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XXIV).
The present step is similar to Step A-4, B-5, C-4, D-2, E-3, F-2,
G-2, J-6, K-5 or L-2.
##STR00029##
In the above formula, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6,
R.sup.7, X and Y have the same meanings as defined above.
Step N is a step to produce Compound (Is) of the present invention
or a compound represented by the formula (XXV), in which a hydroxyl
group is protected, by dechlorinating a 6-chloropyridazine
derivative represented by the formula (Ik) or (XIX), and further a
step to produce Compound (It) of the present invention by removing
the protective group of Compound (XXV).
(Step N-1)
Step N-1 is a step to produce Compound (Is) of the present
invention or a compound represented by the formula (XXV), in which
a hydroxyl group is protected, by reacting Compound (Ik) or (XIX)
with a reducing agent in the presence or absence of a solvent.
The present step can be carried out in accordance with Step J-1 or
K-2.
(Step N-2)
Step N-2 is a step to produce Compound (It) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XXV).
The present step is similar to Step A-4, B-5, C-4, D-2, E-3, F-2,
G-2, J-6, K-5, L-2 or M-2.
##STR00030##
In the above formula, R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.6
and R.sup.7 have the same meanings as defined above.
Step O is a step to produce Compound (Iu) of the present invention
by reacting a 3,4-dichloropyridazine derivative represented by the
formula (XXVI) with a catechol derivative represented by the
formula (XXVII) and then subjecting the resulting material to
hydrolysis.
(Step O-1)
Step O-1 is a step to produce a condensed compound represented by
the formula (XXVIII) by reacting Compound (XXVI) with Compound
(XXVII) in the presence or absence of a solvent, and if necessary,
in the presence of a base.
The present step can be carried out in accordance with Step A-1,
B-2, D-1 or E-2, and an amount of the base to be used is generally
1 to 10 mols, preferably 2 to 6 mols based on 1 mol of Compound
(XXVI).
(Step O-2)
Step O-2 is a step to produce Compound (Iu) of the present
invention by subjecting Compound (XXVIII) to hydrolysis.
The present step can be carried out in accordance with the case
where Y is a hydrogen atom in Step A-3, B-4 or C-3, and a reaction
temperature is preferably 80.degree. C. to 100.degree. C.
##STR00031##
In the above formula, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6
and R.sup.7 have the same meanings as defined above.
Step P is a step to produce Compound (Iv) of the present invention
or a compound represented by the formula (XXXI), in which a
hydroxyl group is protected, by selectively subjecting 6-position
of a 4,6-dichloropyridazine derivative represented by the formula
(Va) to hydrolysis to prepare Compound (XXIX), then, brominating
4,6-positions thereof with phosphorus oxybromide, and then
selectively reacting an oxygen nucleophilic agent at 4-position
thereof, and a step to produce Compound (Iw) of the present
invention by removing the protective group of Compound (XXXI).
(Step P-1)
Step P-1 is a step to produce a compound represented by the formula
(XXIX) by subjecting Compound (Va) to hydrolysis in the presence or
absence of a solvent and in the presence of an acid to selectively
convert a chlorine atom at the 6-position into a hydroxyl
group.
An acid to be used is not specifically limited so long as it is an
acid showing a pH of 6 or less, and for example, it may be organic
acids such as formic acid, acetic acid, oxalic acid, propionic
acid, succinic acid, maleic acid, fumalic acid, benzoic acid, etc.;
mineral acids such as hydrofluoric acid, hydrochloric acid,
hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid,
phosphoric acid, etc.; or Lewis acids such as aluminum chloride,
iron chloride, titanium chloride, boron trifluoride, etc.,
preferably organic acids, more preferably formic acid or acetic
acid.
The present step is carried out preferably in the presence of a
metal salt of an acid.
The metal salt of an acid to be used may inclide, for example,
alkali metal salts of an organic acid such as sodium formate,
potassium formate, lithium acetate, sodium acetate, potassium
acetate, cesium acetate, sodium benzoate, etc.; alkaline earth
metal salts of an organic acid such as magnesium formate, calcium
formate, magnesium acetate, calcium acetate, magnesium benzoate,
etc.; alkali metal salts or alkaline earth metal salts of carbonic
acid such as sodium carbonate, potassium carbonate, calcium
carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate,
etc.; or alkali metal salts or alkaline earth metal salts of a
mineral acid such as sodium fluoride, potassium fluoride, sodium
chloride, potassium chloride, sodium bromide, potassium bromide,
sodium iodide, potassium iodide, sodium sulfate, sodium hydrogen
sulfate, potassium sulfate, potassium hydrogen sulfate, magnesium
sulfate, sodium phosphate, disodium hydrogen phosphate, sodium
dihydrogen phosphate, potassium phosphate, dipotassium hydrogen
phosphate, potassium dihydrogen phosphate, etc., preferably alkali
metal salts of an organic acid, more preferably sodium formate,
potassium formate, sodium acetate or potassium acetate.
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be water; alcohols
such as methanol, ethanol, t-butanol, etc.; ketones such as
acetone, methyl isobutyl ketone, etc.; nitriles such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; organic acids
such as formic acid, acetic acid, propionic acid, etc.; or a mixed
solvent of the above, preferably water, nitriles, ethers, amides,
sulfoxides or organic acids, more preferably water, acetonitrile,
tetrahydrofuran, dioxane, dimethylformamide, dimethylsulfoxide,
formic acid or acetic acid.
The reaction temperature may vary depending on the starting
compounds, reaction reagents and a kind of the solvent to be used,
etc., and is generally -90.degree. C. to 200.degree. C., preferably
0.degree. C. to 150.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually, 5 minutes to 24 hours,
preferably 15 minutes to 12 hours.
(Step P-2)
Step P-2 is a step to produce Compound (XXX) by reacting Compound
(XXIX) with phosphorus oxybromide in the presence or absence of a
solvent.
An amount of the phosphorus oxybromide to be used in the present
step is generally 0.5 to 100 mols, preferably 1 to 10 mols based on
1 mol of Compound (XXIX).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be ketones such as
acetone, methyl isobutyl ketone, etc.; nitriles such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; amides such as dimethylformamide, dimethylacetamide,
etc.; sulfoxides such as dimethylsulfoxide, etc.; aliphatic
hydrocarbons such as hexane, cyclohexane, etc.; or a mixed solvent
of the above, preferably halogenated hydrocarbons, more preferably
methylene chloride, chloroform.
The reaction temperature may vary depending on starting materials,
reaction reagents and a kind of the solvent to be used, and usually
-90.degree. C. to 200.degree. C., preferably 0.degree. C. to
100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 72 hours,
preferably 30 minutes to 24 hours.
(Step P-3)
Step P-3 is a step to produce Compound (Iv) of the present
invention or a compound represented by the formula (XXXI), in which
a hydroxyl group is protected, by reacting Compound (XXX) with an
oxygen nucleophilic agent represented by the formula (VI) in the
presence or absence of a solvent, and if necessary, in the presence
of a base.
The present step is similar to Step A-3, B-4, C-3 or J-5.
(Step P-4)
Step P-4 is a step to produce Compound (Iw) of the present
invention by removing the protective group for a hydroxyl group of
Compound (XXXI).
The present step is similar to Step A-4, B-5, C-4, D-2, E-3, F-2,
G-2, J-6, K-5, L-2, M-2 or N-2.
##STR00032##
In the above formula, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5,
R.sup.6 and R.sup.7 have the same meanings as defined above, a
compound represented by the formula (XXXII) represents an oxygen
nucleophilic agent, a sulfur nucleophilic agent or a nitrogen
nucleophilic agent, Z represents a substituent in which a proton is
removed from the oxygen nucleophilic agent, the sulfur nucleophilic
agent or the nitrogen nucleophilic agent, and for example, it may
be an alkoxy group, a thioalkoxy group, a dialkylamino group,
etc.
Step Q is a step to convert a hydroxy isomer represented by the
formula (Ib) of the present invention into an ester derivative
represented by the formula (Iy) of the present invention.
(Step Q-1)
Step Q-1 is a step to produce Compound (Ix) of the present
invention by reacting Compound (Ib) of the present invention with
phosgene in the presence or absence of a solvent.
An amount of the phosgene to be used in the reaction is generally
0.5 to 10 mols, preferably 1 to 3 mols based on 1 mol of Compound
(Ib).
The reaction is preferably carried out in the presence of a
base.
The base to be used is not specifically limited so long as it is a
base generally showing a pH of 8 or more, and for example, alkali
metal hydroxides such as sodium hydroxide, potassium hydroxide,
etc.; alkali metal carbonates such as sodium carbonate, potassium
carbonate, cesium carbonate, etc.; metal alkoxides such as sodium
methoxide, sodium ethoxide, potassium t-butoxide, etc.; alkali
metal hydrides such as sodium hydride, potassium hydride, etc.;
aliphatic tertiary amines such as triethylamine, tributylamine,
diisopropylethylamine, etc.; aliphatic cyclic tertiary amines such
as 1,4-diazabicyclo-[2.2.2]octane (DABCO),
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc.; pyridines such as
pyridine, collidine, 4-(N,N-dimethylamino)pyridine, etc.; or,
organic metal bases such as n-butyl lithiums, s-butyl lithium,
lithium diisopropylamide, sodium bis(trimehylsilyl)amide, lithium
bis(trimethylsilyl)amide, etc., preferably aliphatic tertiary
amines, aliphatic cyclic tertiary amines or pyridines, more
preferably triethylamine, 1,4-diazabicyclo[2.2.2]octane (DABCO),
pyridine or 4-(N,N-dimethylamino)pyridine.
An amount of the base to be used in the reaction is generally 0.5
to 20 mols, preferably 1 to 5 mols based on 1 mol of Compound
(Ib).
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be ketones such as
acetone, methyl isobutyl ketone, etc.; nitriles such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; aliphatic hydrocarbons such as hexane, cyclohexane,
etc.; amides such as dimethylformamide, dimethylacetamide, etc.;
sulfoxides such as dimethylsulfoxide, etc.; or a mixed solvent of
the above, preferably nitriles, halogenated hydrocarbons or ethers,
more preferably acetonitrile or methylene chloride.
The reaction temperature may vary mainly depending on starting
materials, reaction reagents and a kind of the solvent to be used,
and usually -90.degree. C. to 200.degree. C., preferably 0.degree.
C. to 100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 48 hours,
preferably 15 minutes to 12 hours.
(Step Q-2)
Step Q-2 is a step to produce Compound (Iy) of the present
invention by reacting Compound (Ix) of the present invention with a
nucleophilic agent represented by the formula (XXXII) in the
presence or absence of a solvent, and if necessary, in the presence
of a base.
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, and for example, it may be ketones such as
acetone, methyl isobutyl ketone, etc.; nitriles such as
acetonitrile, etc.; esters such as ethyl acetate, etc.; halogenated
hydrocarbons such as methylene chloride, chloroform,
dichloroethane, etc.; ethers such as diethyl ether,
tetrahydrofuran, dioxane, etc.; aromatic hydrocarbons such as
toluene, etc.; aliphatic hydrocarbons such as hexane, cyclohexane,
etc.; amides such as dimethylformamide, dimethylacetamide, etc.;
sulfoxides such as dimethylsulfoxide, etc.; or a mixed solvent of
the above, preferably nitriles, halogenated hydrocarbons or ethers,
more preferably acetonitrile or methylene chloride.
The base to be used is not specifically limited so long as it is a
base generally showing a pH of 8 or more, and for example, alkali
metal hydroxides such as sodium hydroxide, potassium hydroxide,
etc.; alkali metal carbonates such as sodium carbonate, potassium
carbonate, cesium carbonate, etc.; metal alkoxides such as sodium
methoxide, sodium ethoxide, potassium t-butoxide, etc.; alkali
metal hydrides such as sodium hydride, potassium hydride, etc.;
aliphatic tertiary amines such as triethylamine, tributylamine,
diisopropylethylamine, etc.; aliphatic cyclic tertiary amines such
as 1,4-diazabicyclo-[2.2.2]octane (DABCO),
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc.; pyridines such as
pyridine, collidine, 4-(N,N-dimethylamino)pyridine, etc.; or
organic metal bases such as n-butyl lithiums, s-butyl lithium,
lithium diisopropylamide, sodium bis(trimehylsilyl)amide, lithium
bis(trimethylsilyl)amide, etc., preferably aliphatic tertiary
amines, aliphatic cyclic tertiary amines or pyridines, more
preferably triethylamine, 1,4-diazabicyclo[2.2.2]octane (DABCO),
pyridine or 4-(N,N-dimethylamino)pyridine.
An amount of the base to be used in the reaction is generally 0.5
to 20 mols, preferably 1 to 5 mols based on 1 mol of Compound
(Ix).
The nucleophilic agent (XXXII) to be used in the reaction is not
specifically limited so long as it can substitute a chlorine atom
of chlorocarbonic acid ester (Ix), and the oxygen nucleophilic
agent may include, for example, alcohols such as methanol, ethanol,
propanol, etc.; or phenols such as phenol, 4-chlorophenol, etc.,
also, the sulfur nucleophilic agent may include, for example,
thiols such as methanethiol, ethanethiol, propanethiol, etc.; or
thiophenols such as thiophenol, etc., and, the nitrogen
nucleophilic agent may include, for example, aliphatic linear
amines such as methylamine, dimethylamine, diethylamine,
methyl(t-butyl)amine, methyl(cyanomethyl)amine,
methyl(ethoxycarbonylmethyl)amine, bis(cyanomethyl)amine,
bis(2-cyanoethyl)amine, bis(ethoxycarbonylmethyl)amine,
bis(2-methoxyethyl)amine, bis(2-ethoxyethyl)amine,
bis(2-chloroethyl)amine, N,O-dimethylhydroxylamine, etc.; aromatic
amines such as methyl(phenyl)amine, methyl(pyridyl)amine, etc.;
aliphatic cyclic amines such as aziridine, azetidine, pyrrolidine,
piperidine, morpholine, thiomorpholine, N-methylpiperazine,
N-phenylpiperazine, 2-methoxycarbonylpyrrolidine,
3-hydroxypyrrolidine, 4-bromopiperidine, 4-methylpiperidine,
2,2,6,6-tetramethylpiperidine, 2-ethoxycarbonylpiperidine,
4-ethoxycarbonylpiperidine, 2,6-dimethyl morpholine,
1,2,3,4-tetrahydroisoquinoline, etc.; aromatic cyclic amines such
as carbazole, 2,5-dimethylpyrrole, etc., preferably methanol,
ethanol, methanethiol, ethanethiol, methylamine, dimethylamine,
methyl(cyanomethyl)amine, methyl(ethoxycarbonylmethyl)amine,
bis(cyanomethyl)amine, bis(2-cyanoethyl)amine,
bis(ethoxycarbonylmethyl)amine, bis(2-methoxyethyl)amine,
bis(2-ethoxyethyl)amine, bis(2-chloroethyl)amine,
N,O-dimethylhydroxylamine, methyl(pyridyl)amine, azetidine,
pyrrolidine, piperidine, morpholine, thio morpholine,
N-methylpiperazine, 2-methoxycarbonylpyrrolidine,
3-hydroxypyrrolidine, 2-ethoxycarbonylpiperidine,
4-ethoxycarbonylpiperidine, 2,6-dimethyl morpholine,
2,5-dimethylpyrrole, more preferably dimethylamine,
methyl(cyanomethyl)amine, methyl(ethoxycarbonylmethyl)amine,
bis(cyanomethyl)amine, bis(ethoxycarbonylmethyl)amine,
bis(2-methoxyethyl)amine, bis(2-ethoxyethyl)amine,
N,O-dimethylhydroxylamine, azetidine, morpholine, thiomorpholine,
N-methylpiperazine, 2-methoxycarbonylpyrrolidine,
3-hydroxypyrrolidine, 2-ethoxycarbonylpiperidine,
4-ethoxycarbonylpiperidine, 2,6-dimethyl morpholine.
An amount of the nucleophilic agent to be used in the reaction is
generally 0.5 to 20 mols, preferably 1 to 5 mols based on 1 mol of
Compound (Ix).
The reaction temperature may vary mainly depending on starting
materials, reaction reagents and a kind of the solvent to be used,
and usually -90.degree. C. to 200.degree. C., preferably 0.degree.
C. to 100.degree. C.
The reaction time may vary mainly depending on a reaction
temperature, starting materials, reaction reagents and a kind of
the solvent to be used, and usually 5 minutes to 48 hours,
preferably 15 minutes to 12 hours.
Incidentally, after completion of the above-mentioned respective
steps, and before the steps subsequent thereto, the functional
group(s) in R.sup.1 to R.sup.7 of the desired compound of the
respective steps can be converted to the other functional group so
long as it is within the definitions for R.sup.1 to R.sup.7.
Also, in Steps A-1, B-2, D-1 and E-2, when at least one of R.sup.1
and R.sup.2 is a chlorine atom, depending on the reaction
conditions, in the Step, a chlorine atom of R.sup.1 or R.sup.2 is
substituted by the group
##STR00033## in some cases, and further, in Steps A-3, B-4, C-3 and
J-5, when at least either one of R.sup.1 and R.sup.2 is a chlorine
atom, depending on the reaction conditions, in the Step, a chlorine
atom of R.sup.1 or R.sup.2 is substituted by the group OY in some
cases, and further, in Step P-3, a bromine atom at the 6-position
of the pyridazine ring or a chlorine atom of R.sup.2 when R.sup.2
is a chlorine atom is substituted by the group OY in some
cases.
Starting Compound (II) in Step A and B may be used those
commercially available, or may be produced by the method disclosed
in, for example, Kogyo Kagaku Zasshi (Journal of Industrial
Chemistry), 1971, vol. 74, No. 7, pp. 1490-1491; Tetrahedron, 1999,
vol. 55, No. 52, pp. 15067 to 15070; The Journal of Organic
Chemistry, 1963, vol. 28, pp. 218 to 221 or in accordance with
these methods.
The starting Compound (X) of Steps D and E can be produced by the
method disclosed in, for example, Helvetica Chimica Acta, 1956,
vol. 39, pp. 1755 to 1764; Monatshefte fur Chemie, 1968, vol. 99,
pp. 15-81 (in the present specification, the letter u in
Monatshefte fur Chemie represents u-umlaut.); German Patent
1,912,472, Nov. 12, 1970 (filed on Apr. 12, 1969) (Ger. Offen.
1,912,472, 12 Nov. 1970, Appl. 12 Mar. 1969), or in accordance with
these methods.
The phenol Compound (III) to be used in Steps A, B, D and E may be
used those commercially available, or may be produced by using the
conventionally known method or in accordance with these
methods.
2-Isobutylphenol can be produced by the method disclosed in, for
example, Canadian Journal of Chemistry, 1956, vol. 34, pp.
851-854.
2-Pentylphenol can be produced by the method disclosed in, for
example, Tetrahedron Letters, 1989, vol. 30, No. 35, pp.
4741-4744.
2-Hexylphenol can be produced by the method disclosed in, for
example, Journal of the Chemical Society: Parkin transaction I,
2000, vol. 7, pp. 1109-1116 (coversion of vinyl group into hexyl
group), and Journal of Medicinal Chemistry, 1977, vol. 20, No. 10,
pp. 1317-1323 (conversion of phenylmethyl ether into phenol,
demethylation reaction) from commercially available
1-methoxy-2-vinylbenzene.
2-Cyclopropylphenol can be produced by the method disclosed in, for
example, Bioorganic & Medicinal Chemistry, 1997, vol. 5, No.
10, pp. 1959-1968.
2-(1-Methylcyclopropyl)phenol can be produced in accordance with
the method disclosed in, for example, from commercially available
1-(2-methoxyphenyl)ethanone, The Journal of Organic Chemistry,
1963, vol. 28, p. 1128 or Synthetic Communications, 1985, vol. 15,
No. 10, pp. 855-864 (conversion of carbonyl group into olefin,
Wittg reaction), and by the method disclosed in Organic Reactions,
1973, vol. 20, pp. 1-131 or Journal of the American Chemical
Society, 1975, vol. 97, p. 3428 or Tetrahedron Letters, 1998, vol.
39, pp. 8621-8624 (construction of cyclopropyl group, Simmons-Smith
reaction), and by the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
2-(1-Ethylcyclopropyl)phenol can be produced in accordance with the
method disclosed in, for example, from commercially available
1-(2-methoxyphenyl)-1-propanone, The Journal of Organic Chemistry,
1963, vol. 28, p. 1128 or Synthetic Communications, 1985, vol. 15,
No. 10, pp. 855-864 (conversion of carbonyl group into olefin,
Wittg reaction), and by the method disclosed in Organic Reactions,
1973, vol. 20, pp. 1-131 or Journal of the American Chemical
Society, 1975, vol. 97, p. 3428 or Tetrahedron Letters, 1998, vol.
39, pp. 8621-8624 (construction of cyclopropyl group, Simmons-Smith
reaction), and by the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
2-(1-Cyclopropylcyclopropyl)phenol can be produced in accordance
with the method disclosed in, for example, Organic Synthesis,
Collective Volume, vol. 4, pp. 836-838 (conversion of phenol into
phenyl methyl ether, methylation reaction), and the method
disclosed in The Journal of Organic Chemistry, 1963, vol. 28, p.
1128 or Synthetic Communications, 1985, vol. 15, No. 10, pp.
855-864 (conversion of carbonyl group into olefin, Wittg reaction),
and the method disclosed in Organic Reactions, 1973, vol. 20, pp.
1-131 or Journal of the American Chemical Society, 1975, vol. 97,
p. 3428 or Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624
(construction of cyclopropyl group, Simmons-Smith reaction), and by
the method disclosed in Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction) from
cyclopropyl(2-hydroxyphenyl)methanone produced by the method
disclosed in Journal of the Chemical Society: Parkin transaction I,
1990, pp. 689-693 from commercially available
2,3-dihydro-4H-chromen-4-one.
1-(2-Hydroxyphenyl)cyclopropanecarbonitrile can be produced by
producing 1-(2-methoxyphenyl)cyclopropanecarbonitrile in accordance
with the method disclosed in, for example, Journal of the American
Chemical Society, 2000, vol. 122, No. 4, pp. 712-713, and by the
method disclosed in Organic Synthesis, Collective Volume, vol. 5,
pp. 412-414 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-(1-Phenylcyclopropyl)phenol can be produced in accordance with
the method disclosed in, for example, from commercially available
1-(2-methoxyphenyl)(phenyl)methanone, The Journal of Organic
Chemistry, 1963, vol. 28, p. 1128 or Synthetic Communications,
1985, vol. 15, No. 10, pp. 855-864 (conversion of carbonyl group
into olefin, Wittg reaction), and by the method disclosed in
Organic Reactions, 1973, vol. 20, pp. 1-131 or Journal of the
American Chemical Society, 1975, vol. 97, p. 3428 or Tetrahedron
Letters, 1998, vol. 39, pp. 8621-8624 (construction of cyclopropyl
group, Simmons-Smith reaction), and by the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-(2-Methylcyclopropyl)phenol can be produced in accordance with
the method disclosed in, for example, from commercially available
1-(chloromethyl)-2-methoxybenzene, Journal of the American Chemical
Society, 1973, vol. 95, No. 2, pp. 581-582 (construction of
cyclopropyl group), and by the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
2-(2,2-Dimethylcyclopropyl)phenol can be produced in accordance
with the method disclosed in, for example, from commercially
available 1-(chloromethyl)-2-methoxybenzene, Journal of the
American Chemical Society, 1973, vol. 95, No. 2, pp. 581-582
(construction of cyclopropyl group), and by the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-[(Cis-2,cis-3-dimethyl)-ref-1-cyclopropyl]phenol can be produced
in accordance with the method disclosed in, for example, from
commercially available 1-(chloromethyl)-2-methoxybenzene, Journal
of the American Chemical Society, 1973, vol. 95, No. 2, pp. 581-582
(construction of cyclopropyl group), and by the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-[(Cis-2,trans-3-dimethyl)-ref-1-cyclopropyl]phenol can be
produced in accordance with the method disclosed in, for example,
from commercially available 1-(chloromethyl)-2-methoxybenzene,
Journal of the American Chemical Society, 1973, vol. 95, No. 2, pp.
581-582 (construction of cyclopropyl group), and by the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2-[(Trans-2,trans-3-dimethyl)-ref-1-cyclopropyl]phenol can be
produced in accordance with the method disclosed in, for example,
from commercially available 1-(chloromethyl)-2-methoxybenzene,
Journal of the American Chemical Society, 1973, vol. 95, No. 2, pp.
581-582 (construction of cyclopropyl group), and by the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2-[(Ref-1,cis-5,cis-6)-bicyclo[3.1.0]hexa-6-yl]phenol can be
produced in accordance with the method disclosed in, for example,
from commercially available 1-(chloromethyl)-2-methoxybenzene,
Journal of the American Chemical Society, 1973, vol. 95, No. 2, pp.
581-582 (construction of cyclopropyl group), and by the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2-[(Ref-1,cis-5,trans-6)-bicyclo[3.1.0]hexa-6-yl]phenol can be
produced in accordance with the method disclosed in, for example,
from commercially available 1-(chloromethyl)-2-methoxybenzene,
Journal of the American Chemical Society, 1973, vol. 95, No. 2, pp.
581-582 (construction of cyclopropyl group), and by the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2-[(Ref-1,cis-6,cis-7)-bicyclo[4.1.0]hept-7-yl]phenol can be
produced in accordance with the method disclosed in, for example,
from commercially available 1-(chloromethyl)-2-methoxybenzene,
Journal of the American Chemical Society, 1973, vol. 95, No. 2, pp.
581-582 (construction of cyclopropyl group), and by the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2-[(Ref-1,cis-6,trans-7)-bicyclo[4.1.0]hept-7-yl]phenol can be
produced in accordance with the method disclosed in, for example,
from commercially available 1-(chloromethyl)-2-methoxybenzene,
Journal of the American Chemical Society, 1973, vol. 95, No. 2, pp.
581-582 (construction of cyclopropyl group), and by the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2-[(2,2,Cis-3-trimethyl)-ref-1-cyclopropyl]phenol can be produced
in accordance with the method disclosed in, for example, from
commercially available 1-(chloromethyl)-2-methoxybenzene, Journal
of the American Chemical Society, 1973, vol. 95, No. 2, pp. 581-582
(construction of cyclopropyl group), and by the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-[(2,2,trans-3-trimethyl)-ref-1-cyclopropyl]phenol can be produced
in accordance with the method disclosed in, for example, from
commercially available 1-(chloromethyl)-2-methoxybenzene, Journal
of the American Chemical Society, 1973, vol. 95, No. 2, pp. 581-582
(construction of cyclopropyl group), and by the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-Cyclobutylphenol can be produced by the method disclosed in, for
example, German Patent DE-2825388.
1-(2-Hydroxyphenyl)cyclobutancarbonitrile can be produced by the
method disclosed in, for example, Pharmaceutical Chemistry Journal
(English Translation), 1980, vol. 14, No. 2, pp. 114-118.
1-(2-Hydroxyphenyl)cyclobutanecarboxylic acid can be produced by
the method disclosed in, for example, Pharmaceutical Chemistry
Journal (English Translation), 1980, vol. 14, No. 2, pp.
114-118.
2-(1-Propynyl)phenol can be produced by the method disclosed in,
for example, Journal of the Chemical Society: Parkin transaction I,
1998, pp. 477-484.
2-(Cyclopropylmethyl)phenol can be produced in accordance with the
method disclosed in, for example, Organic Reactions, 1941, vol, 1,
p. 155 (Clemmensen reduction) from
cyclopropyl(2-hydroxyphenyl)methanone which can be produced by the
method disclosed in Journal of the Chemical Society: Parkin
transaction I, 1990, pp. 689-693 from commercially available
2,3-dihydro-4H-chromen-4-one.
2-(Methoxymethyl)phenol can be produced by the method disclosed in,
for example, Tetrahedron Letters, 1999, vol. 40, p. 6049.
2-(Ethoxymethyl)phenol can be produced by the method disclosed in,
for example, Tetrahedron Letters, 1999, vol. 40, p. 6049.
2-(1,3-Dioxolan-2-yl)phenol can be produced by the method disclosed
in, for example, Tetrahedron Letters, 1989, vol. 30, No. 13, pp.
1609-1612.
1-(2-Hydroxyphenyl)ethanone O-methyloxime can be produced in
accordance with the method disclosed in, for example, commercially
available 1-(2-hydroxyphenyl)ethanone, Journal of the American
Chemical Society, 1986, vol. 108, pp. 6016-6023.
3'-(Trifluoromethyl)[1,1'-biphenyl]-2-ol can be produced in
accordance with the method disclosed in, for example, from
commercially available 2-iodophenol and
3-(trifluoromethyl)phenylboronic acid, Chemical Reviews, 1995, vol.
95, pp. 2457-2483 (phenylation reaction, Suzuki-Miyaura coupling
reaction).
2-(1H-pyrrole-1-yl)phenol can be produced by the method disclosed
in, for example, The Journal of Antibiotics, 1994, vol. 47, No. 5,
pp. 602-605.
2-(2-Thienyl)phenol can be produced by the method disclosed in, for
example, Journal of Heterocyclic Chemistry, 1985, vol. 22, pp.
1667-1669.
2-(3-Thienyl)phenol can be produced by the method disclosed in, for
example, Journal of Heterocyclic Chemistry, 1985, vol. 22, pp.
1667-1669.
2-(1H-pyrazol-1-yl)phenol can be produced by the method disclosed
in, for example, Canadian Journal of Chemistry, 1963, vol. 41, pp.
2086-2092.
2-(3,5-Dimethyl-1H-pyrazol-1-yl)phenol can be produced by the
method disclosed in, for example, Heterocycles, 1982, vol. 19, No.
8, pp. 1487-1495.
2-[3-(Trifluoromethyl)-1H-pyrazol-1-yl]phenol can be produced, for
example, by preparing
1-(2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol from
commercially available 1-(2-methoxyphenyl)hydrazine hydrochloride
by the method disclosed in Journal of Fluorine Chemistry 1998, vol.
92, p. 23, and in accordance with the method disclosed in Organic
Synthesis, Collective Volume, vol. 5, pp. 412-414 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
2-[4-(Trifluoromethyl)-1H-pyrazol-1-yl]phenol can be produced, for
example, by preparing
1-(2-methoxyphenyl)-4-(trifluoromethyl)-1H-pyrazole from
commercially available 1-(2-methoxyphenyl)hydrazine hydrochloride
by the method disclosed in Tetrahedron Letters, 1996, vol. 37, No.
11, p. 1829, and in accordance with the method disclosed in Organic
Synthesis, Collective Volume, vol. 5, pp. 412-414 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
2-[5-(Trifluoromethyl)-1H-pyrazol-1-yl]phenol can be produced, for
example, by preparing
1-(2-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole from
commercially available 1-(2-methoxyphenyl)hydrazine hydrochloride
by the method disclosed in Journal of Fluorine Chemistry, 1998,
vol. 92, p. 23, and in accordance with the method disclosed in
Organic Synthesis, Collective Volume, vol. 5, pp. 412-414
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
5-(2-Hydroxyphenyl)-N,N-dimethyl-1H-pyrazol-1-sulfonamide can be
produced, for example, from
5-(5-chloro-2-hydroxyphenyl)-N,N-dimethyl-1H-pyrazol-1-sulfonamide,
which can be produced from commercially available
4-chloro-2-(1H-pyrazol-5-yl)phenol in accordance with the method
disclosed in Journal of Medicinal Chemistry, 1998, vol. 41, No. 12,
pp. 2019-2028, in accordance with the method disclosed in, Jikken
Kagaku Koza (Experimental Chemistry Lecture), 4th Edition, vol. 26,
pp. 251-266 (catalytic hydrogenation reaction).
3-(2-Hydroxyphenyl)-N,N-dimethyl-1H-pyrazol-1-sulfonamide can be
produced, for example, from
3-(5-chloro-2-hydroxyphenyl)-N,N-dimethyl-1H-pyrazol-1-sulfonamide,
which can be produced from commercially available
4-chloro-2-(1H-pyrazol-5-yl)phenol in accordance with the method
disclosed in Journal of Medicinal Chemistry, 1998, vol. 41, No. 12,
pp. 2019-2028, in accordance with the method disclosed in, Jikken
Kagaku Koza (Experimental Chemistry Lecture), 4th Edition, vol. 26,
pp. 251-266 (catalytic hydrogenation reaction).
2-(4-Methyl-1,3-thiazol-2-yl)phenol can be produced by the method
disclosed in, for example, from commercially available
2-hydroxybenzonitrile, Japanese Provisional Patent Publication No.
11-60552 (thioamidation reaction of a cyano group), and the method
disclosed in Liebigs Annalen der Chemie, 1890, vol. 259, p.
236.
2-(1,3-Benzothiazol-2-yl)phenol can be produced by the method
disclosed in, for example, The Journal of Organic Chemistry, 1970,
vol. 35, pp. 3147-3149.
2-(Dimethylamino)phenol can be produced by the method disclosed in,
for example, Journal of Medicinal Chemistry, 1998, vol. 41, pp.
4800-4818.
2-(2-Methoxyethoxy)phenol can be produced in accordance with the
method disclosed in, for example, Journal of the Chemical Society:
Parkin transaction I, 1980, pp. 756-758 from commercially available
pyrocatechol.
2-(Isopropylsulfanyl)phenol can be produced by the method disclosed
in, for example, Tetrahedron, 1970, vol. 26, pp. 4449-4471.
3-Cyclopropylphenol can be produced by the method disclosed in, for
example, from commercially available 1-bromo-3-methoxybenzene,
Tetrahedron Letters, 2000, vol. 41, pp. 4251-4255 (construction of
cyclopropyl group, Suzuki-Miyaura coupling reaction), and in
accordance with the method disclosed in Bioscience, Biotechnology,
and Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
3-(2-Furyl)phenol can be produced, for example, by producing
2-(3-methoxyphenyl)furan by the method disclosed in The Journal of
Organic Chemistry, 1993, vol. 58, No. 17, pp. 4722-4726, and in
accordance with the method disclosed in Bioscience, Biotechnology,
and Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
4-Cyclopropylphenol can be produced in accordance with the method
disclosed in, for example, from commercially available
1-bromo-4-methoxybenzene, Tetrahedron Letters, 2000, vol. 41, pp.
4251-4255 (construction of cyclopropyl group, Suzuki-Miyaura
coupling reaction), and by the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
2-Bromo-3-methylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-methoxy-6-methylaniline, Organic Synthesis, Collective Volume,
vol. 3, pp. 185-187 or the method disclosed in The Journal of
Organic Chemistry, 1977, vol. 42, pp. 2426-2430 (conversion of
anilines into bromobenzene, Sandmeyer reaction, etc.) and,
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
3-Fluoro-2-methylphenol can be produced in accordance with the
method disclosed in Journal of the Chemical Society: Parkin
transaction I, 1974, p. 1353 from commercially available
3-fluoro-2-methylbenzaldehyde.
3-Chloro-2-methylphenol can be produced in accordance with the
method disclosed in Organic Synthesis, Collective Volume, vol. 5,
pp. 412-414 (conversion of phenylmethyl ether into phenol,
demethylation reaction) from commercially available
1-chloro-3-methoxy-2-methylbenzene.
3-Methoxy-2-methylphenol can be produced in accordance with the
method disclosed in, Organic Synthesis, Collective Volume, vol. 4,
pp. 836-838 (conversion of phenol into phenyl methyl ether,
methylation reaction) from commercially available
2-methyl-1,3-benzene diol.
2-Cyclopropyl-3-methylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-methoxy-6-methylaniline, Organic Synthesis, Collective Volume,
vol. 3, pp. 185-187 or the method disclosed in The Journal of
Organic Chemistry, 1977, vol. 42, pp. 2426-2430 (conversion of
anilines into bromobenzene, Sandmeyer reaction, etc.), and the
method disclosed in Tetrahedron Letters, 1979, vol. 20, pp.
4159-4162 or the method disclosed in Tetrahedron, 1997, vol. 53,
No. 43, pp. 14599-14614 or the method disclosed in Bulletin of the
Chemical Society of Japan, 1971, vol. 44, pp. 2237-2248 (conversion
reaction of aromatic bromide into aromatic aldehyde), and the
method disclosed in The Journal of Organic Chemistry, 1963, vol.
2.8, p. 1128 or Synthetic Communications, 1985, vol. 15, No. 10,
pp. 855-864 (conversion of carbonyl group into olefin, Wittg
reaction), and the method disclosed in Organic Reactions, 1973,
vol. 20, pp. 1-131 or Journal of the American Chemical Society,
1975, vol. 97, 3428 or the method disclosed in Tetrahedron Letters,
1998, vol. 39, pp. 8621-8624 (construction of cyclopropyl group,
Simmons-Smith reaction), and the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
2-Cyclopropyl-3-methoxyphenol can be produced in accordance with
the method disclosed in, for example, from commercially available
2,6-dimethoxybenzaldehyde, The Journal of Organic Chemistry, 1963,
vol. 28, p. 1128 or Synthetic Communications, 1985, vol. 15, No.
10, pp. 855-864 (conversion of carbonyl group into olefin, Wittg
reaction), and the method disclosed in Organic Reactions, 1973,
vol. 20, pp. 1-131 or Journal of the American Chemical Society,
1975, vol. 97, p. 3428 or Tetrahedron Letters, 1998, vol. 39, pp.
8621-8624 (construction of cyclopropyl group, Simmons-Smith
reaction), and the method disclosed in Bioscience, Biotechnology,
and Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
4-indanol can be produced in accordance with the method disclosed
in, for example, Organic Reactions, 1941, vol. 1, p. 155
(Clemmensen reduction) from commercially available
4-hydroxy-1-indanone.
3-methyl-4-indanol can be produced by the method disclosed in, for
example, Journal of Applied Chemistry, 1959, vol. 9, pp. 629 and
637.
1-Methyl-4-indanol can be produced by the method disclosed in, for
example, Journal of the Chemical Society, 1961, pp. 2773-2777.
2,2-Dimethyl-4-indanol can be produced by the method disclosed in,
for example, Journal of Chemical Research Miniprint, 1985, vol. 8,
pp. 2724-2747.
Spiro[cyclopropane-1,3'-(2',3'-dihydro-1'H-inden-4'-ol)] can be
produced in accordance with the method disclosed in, for example,
from commercially available 2,3-dihydro-4H-chromen-4-ol, Bioorganic
and Medicinal Chemistry, 1999, vol. 7, No. 12, pp. 2801-2810
(synthesis of 7-hydroxy-1-indanone), and the method disclosed in
Organic Synthesis, Collective Volume vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction), and the method disclosed in The Journal of Organic
Chemistry, 1963, vol. 28, p. 1128 or Synthetic Communications,
1985, vol. 15, No. 10, pp. 855-864 (conversion of carbonyl group
into olefin, Wittg reaction), and the method disclosed in Organic
Reactions, 1973, vol. 20, pp. 1-131 or Journal of the American
Chemical Society, 1975, vol. 97, p. 3428 or Tetrahedron Letters,
1998, vol. 39, pp. 8621-8624 (construction of cyclopropyl group,
Simmons-Smith reaction), and the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
7-hydroxy-2,3-dihydro-1H-inden-1-one O-methyloxime can be produced
in accordance with the method disclosed in, for example, from
commercially available 2,3-dihydro-4H-chromen-4-ol, Bioorganic and
Medicinal Chemistry, 1999, vol. 7, No. 12, pp. 2801-2810 (synthesis
of 7-hydroxy-1-indanone), and the method disclosed in Organic
Synthesis, Collective Volume vol. 4, pp. 836-838 (conversion of
phenol into phenyl methyl ether, methylation reaction), and the
method disclosed in Chemical Pharmaceutical Bulletin, 1988, vol.
36, No. 8, pp. 3134-3137 (conversion of carbonyl group into oxime),
and the method disclosed in Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
2,3-Dihydro-1-benzofuran-4-ol can be produced by the method
disclosed in, for example, Journal of the Chemical Society, 1948,
p. 894 (reduction of olefin) from 1-benzofuran-4-ol which is
obtained by the method disclosed in Helvetica Chimica Acta, 1933,
vol. 16, pp. 121-129.
3-Methyl-2,3-dihydro-1-benzofuran-4-ol can be produced in
accordance with the method disclosed in, for example, Journal of
the Chemical Society, 1948, p. 894 (reduction of olefin) from
3-methyl-1-benzofuran-4-ol which is obtained by the method
disclosed in Journal of the Chemical Society, 1951, pp.
3229-3234.
1-Benzofuran-4-ol can be produced by the method disclosed in, for
example, Helvetica Chimica Acta, 1933, vol. 16, pp. 121-129.
3-Methyl-1-benzofuran-4-ol can be produced by the method disclosed
in, for example, Journal of the Chemical Society, 1951, pp.
3229-3234.
1-Benzothiophen-4-ol can be produced by the method disclosed in,
for example, Journal of the American Chemical Society, 1935, vol.
57, pp. 1611-1615.
2-Methyl-1,3-benzoxazol-4-ol can be produced in accordance with the
method disclosed in, for example, Journal of Medicinal Chemistry,
1987, vol. 30, No. 1, pp. 62-67.
2,3-Dihydro-1-benzofuran-7-ol can be produced in accordance with
the method disclosed in, for example, from commercially available
7-methoxy-1-benzofuran, Journal of the Chemical Society, 1948, p.
894 (hydrogenation reaction of benzofuran), and the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
1-Benzofuran-7-ol can be produced in accordance with the method
disclosed in, for example, from commercially available
7-methoxy-1-benzofuran, Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
1,3-Benzodioxol-4-ol can be produced by the method disclosed in,
for example, Chemical Pharmaceutical Bulletin, 1981, vol. 29, No.
10, pp. 2893-2898 from commercially available 1,2,3-benzene
triol.
2,3-Dihydro-1,4-benzodioxyn-5-ol can be produced by the method
disclosed in, for example, Journal of the Chemical Society: Parkin
transaction I, 1988, pp. 511 to 520 from commercially available
1,2,3-benzene triol.
2-Methyl-1,3-benzoxazol-7-ol can be produced in accordance with the
method disclosed in, for example, Liebigs Annalen der Chemie, 1957,
vol. 608, p. 128 (reduction of a nitro group into an amino group),
and the method disclosed in Journal of Medicinal Chemistry, 1987,
vol. 30, No. 1, pp. 62-67 from commercially available
3-nitro-1,2-benzene diol.
2-Bromo-4-tert-butylphenol can be produced by the method disclosed
in, for example, Tetrahedron, 1999, vol. 55, No. 28, pp.
8377-8384.
2-Ethyl-4-iodophenol can be produced by the method disclosed in,
The Journal of Organic Chemistry, 1951, vol. 16, pp. 1117-1120 from
commercially available 2-ethylphenol.
4-Bromo-2-isopropylphenol can be produced by the method disclosed
in, for example, Journal of Medicinal Chemistry, 1971, vol. 14, No.
9, pp. 789-792.
3-Cyclopropyl-4-methylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-bromo-1-methoxy-4-methylbenzene, Tetrahedron Letters, 2000, vol.
41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction) and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
5-(Dimethylamino)-2-methylphenol can be produced by the method
disclosed in, for example, Journal of the Chemical Society, 1947,
pp. 182-191.
5-Methoxy-2-methylphenol can be produced by the method disclosed
in, for example, Chemical Abstracts, 1938, p. 2519.
2-Ethyl-5-methoxyphenol can be produced by the method disclosed in,
for example, Chemical and Pharmaceutical Bulletin, 1979, vol. 27,
No. 6, pp. 1490-1494.
2,5-Diisopropylphenol can be produced by the method disclosed in,
for example, The Journal of Organic Chemistry, 1980, vol. 45, No.
22, pp. 4326-4329.
2-Cyclopropyl-5-fluorophenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-bromo-5-fluorophenol, Helvetica Chimica Acta, 1992, vol. 75, p.
457 (conversion of phenol into phenylmethoxymethyl ether,
methoxymethylation reaction), and the method disclosed in
Tetrahedron Letters, 2000, vol. 41, pp. 4251-4255 (construction of
cyclopropyl group, Suzuki-Miyaura coupling reaction), and the
method disclosed in Tetrahedron, 1998, vol. 54, pp. 15861-15869
(conversion of phenylmethoxymethyl ether into phenol,
demethoxymethylation reaction).
5-Chloro-2-cyclopropylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
4-chloro-2-methoxyphenol, The Journal of Organic Chemistry, 1997,
vol. 62, No. 2, pp. 261-274 (trifluoromethanesulfonylation of
phenol), and the method disclosed in Tetrahedron Letters, 2000,
vol. 41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-Cyclopropyl-5-methylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-methoxy-4-methylphenol, The Journal of Organic Chemistry, 1997,
vol. 62, No. 2, pp. 261-274 (trifluoromethanesulfonylation of
phenol), and the method disclosed in Tetrahedron Letters, 2000,
vol. 41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-Cyclopropyl-5-ethylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
4-ethyl-2-methoxyphenol, The Journal of Organic Chemistry, 1997,
vol. 62, No. 2, pp. 261-274 (trifluoromethanesulfonylation of
phenol), and the method disclosed in Tetrahedron Letters, 2000,
vol. 41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-Cyclopropyl-5-isopropylphenol can be produced in accordance with
the method disclosed in, for example, from commercially available
3-isopropylphenol, Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and the method disclosed in
Helvetica Chimica Acta, 1992, vol. 75, p. 457 (conversion of phenol
into phenylmethoxymethyl ether, methoxymethylation reaction), and
the method disclosed in Tetrahedron Letters, 2000, vol. 41, pp.
4251-4255 (construction of cyclopropyl group, Suzuki-Miyaura
coupling reaction), and the method disclosed in Tetrahedron, 1998,
vol. 54, pp. 15861-15869 (conversion of phenylmethoxymethyl ether
into phenol, demethoxymethylation reaction).
4-Cyclopropyl-3-hydroxybenzonitrile can be produced in accordance
with the method disclosed in, for example, from commercially
available 4-hydroxy-3-methoxybenzonitrile, The Journal of Organic
Chemistry, 1997, vol. 62, No. 2, pp. 261-274
(trifluoromethanesulfonylation of phenol), and the method disclosed
in Tetrahedron Letters, 2000, vol. 41, pp. 4251-4255 (construction
of cyclopropyl group, Suzuki-Miyaura coupling reaction), and the
method disclosed in Bioscience, Biotechnology, and Biochemistry,
1993, vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
5-Fluoro-2-[(1E)-1-propenyl]phenol can be produced in accordance
with the method disclosed in, for example, Journal of the Chemical
Society: Parkin transaction I, 1994, pp. 1823-1831 (synthesis of
4-fluoro-2-hydroxybenzaldehyde), and the method disclosed in
Organic Synthesis, Collective Volume, vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction), and the method disclosed in Synthetic Communications,
1985, vol. 15, No. 10, pp. 855-864 (conversion of carbonyl group
into olefin, Wittg reaction), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
5-Chloro-2-[(1E)-1-propenyl]phenol can be produced in accordance
with the method disclosed in, for example, The Journal of Organic
Chemistry, 1964, vol. 29, pp. 2693-2698 (synthesis of
4-chloro-2-hydroxybenzaldehyde), and the method disclosed in
Organic Synthesis, Collective Volume, vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction), the method disclosed in Synthetic Communications, 1985,
vol. 15, No. 10, pp. 855-864 (conversion of carbonyl group into
olefin, Wittg reaction), and the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
4-(Dimethylamino)-2-hydroxybenzaldehyde can be produced by the
method disclosed in, for example, German Patent (DE 105103).
5-Chloro-2-methoxyphenol can be produced in accordance with the
method disclosed in, for example, Organic Synthesis, Collective
Volume, vol. 2, pp. 130-133 (conversion of anilines into
chlorobenzene, Sandmeyer reaction, etc.) from commercially
available 5-amino-2-methoxyphenol.
5-Bromo-2-methoxyphenol can be produced in accordance with the
method disclosed in, for example, Organic Synthesis, Collective
Volume, vol. 3, pp. 185-187 or the method disclosed in The Journal
of Organic Chemistry, 1977, vol. 42, pp. 2426-2430 (conversion of
anilines into bromobenzene, Sandmeyer reaction, etc.) from
commercially available 5-amino-2-methoxyphenol.
3-Hydroxy-4-methoxybenzonitrile can be produced by the method
disclosed in, for example, Synthesis, 1998, pp. 329-332 from
commercially available methyl 3,4-dimethoxybenzoate.
2,5-Dimethoxyphenol can be produced by the method disclosed in, for
example, The Journal of Organic Chemistry, 1987, vol. 57, p.
4485.
2-Bromo-6-fluorophenol can be produced in accordance with the
method disclosed in, for example, Tetrahedron Letters, 1998, vol.
39, p. 2947 (bromination reaction of phenol) from commercially
available 2-fluorophenol.
2-Fluoro-6-propylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-fluorophenol, Organic Reactions, 1949, vol. 2, pp. 1-48
(allyllation of phenol, Claisen transition reaction), and the
method disclosed in Journal of the American Chemical Society, 1951,
vol. 73, pp. 4152-4156 (conversion of an allyl group into a propyl
group, hydrogenation reaction).
2-Fluoro-6-isopropylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-isopropyl-6-nitrophenol, Organic Synthesis, Collective Volume
vol. 4, pp. 836-838 (conversion of phenol into phenyl methyl ether,
methylation reaction), the method disclosed in Liebigs Annalen der
Chemie, 1975, vol. 608, p. 128 (Reduction of a nitro group into an
amino group), the method disclosed in Synthesis, 1989, p. 905
(conversion reaction of an amino group into a fluorine atom), and
the method disclosed in Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
2-Cyclopropyl-6-fluorophenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-fluorophenol, Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and the method disclosed in
Helvetica Chemica Acta, 1992, vol. 75, p. 457 (conversion of phenol
into phenylmethoxymethyl ether, methoxymethylation reaction), and
the method disclosed in Tetrahedron Letters, 2000, vol. 41, pp.
4251-4255 (construction of cyclopropyl group, Suzuki-Miyaura
coupling reaction), and the method disclosed in Tetrahedron, 1998,
vol. 54, pp. 15861-15869 (conversion of phenylmethoxymethyl ether
into phenol, demethoxymethylation reaction).
2-Chloro-6-iodophenol can be produced by the method disclosed in,
for example, The Journal of Organic Chemistry, 1988, vol. 53, No.
22, pp. 5281-5287.
2-Chloro-6-ethylphenol can be produced by the method disclosed in,
for example, Journal of Chemical and Engineering Data, 1969, vol.
14, p. 392.
2-Chloro-6-cyclopropylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2-chlorophenol, Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and the method disclosed in
Helvetica Chimica Acta, 1992, vol. 75, p. 457 (conversion of phenol
into phenylmethoxymethyl ether, methoxymethylation reaction), and
the method disclosed in Tetrahedron Letters, 2000, vol. 41, pp.
4251-4255 (construction of cyclopropyl group, Suzuki-Miyaura
coupling reaction), and the method disclosed in Tetrahedron, 1998,
vol. 54, pp. 15861-15869 (conversion of phenylmethoxymethyl ether
into phenol, demethoxymethylation reaction).
2-Chloro-6-(2-methyl-2-propenyl)phenol can be produced in
accordance with the method disclosed in, for example, Organic
Reactions, 1949, vol. 2, pp. 1-48 (allylation of phenol, Claisen
transition reaction) from commercially available
2-chlorophenol.
2-Bromo-6-methylphenol can be produced by the method disclosed in,
for example, Tetrahedron Letters, 1998, vol. 39, p. 2947.
2-Bromo-6-ethylphenol can be produced in accordance with the method
disclosed in, for example, Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol) from commercially available
2-ethylphenol.
2-Bromo-6-cyclopropylphenol can be produced in accordance with the
method disclosed in, for example, from commercially available
2,6-dibromophenol, Organic Synthesis, Collective Volume vol. 4, pp.
836-838 (conversion of phenol into phenyl methyl ether, methylation
reaction), and the method disclosed in Tetrahedron Letters, 2000,
vol. 41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
3-Bromo-2-hydroxybenzonitrile can be produced in accordance with
the method disclosed in, for example, Tetrahedron Letters, 1998,
vol. 39, p. 2947 (bromination reaction of phenol) from commercially
available 2-hydroxybenzonitrile.
2-Bromo-6-methoxyphenol can be produced by the method disclosed in,
for example, Synthesis, 1999, vol. 7, pp. 1127-1134.
2-Iodo-6-methylphenol can be produced by the method disclosed in,
for example, Australian Journal of Chemistry, 1997, vol. 50, No. 7,
pp. 767-770.
2-Ethyl-6-iodophenol can be produced in accordance with the method
disclosed in, Australian Journal of Chemistry, 1997, vol. 50, No.
7, pp. 767-770 (iodation reaction of phenol) from commercially
available 2-ethylphenol.
2-Iodo-6-isopropylphenol can be produced in accordance with the
method disclosed in, Australian Journal of Chemistry, 1997, vol.
50, No. 7, pp. 767-770 (iodation reaction of phenol) from
commercially available 2-isopropylphenol.
2-Isopropyl-6-methylphenol can be produced by the method disclosed
in, for example, Bulletin de la Societe Chemique de France, 1962,
pp. 1700-1705.
2-s-Butyl-6-methylphenol can be produced by the method disclosed
in, for example, Angewandte Chemie, 1957, vol. 69, p. 699, p. 703.
Also, for example, it can be produced in accordance with the method
disclosed in Organic Reactions, 1949, vol. 2, pp. 1-48 (allylation
of phenol, Claisen transition reaction), and Journal of the
American Chemical Society, 1951, vol. 73, pp. 4152-4156 (conversion
of allyl group into propyl group, hydrogenation reaction) from
commercially available 2-methylphenol.
2-Cyclopropyl-6-methylphenol can be produced from commercially
available 2-hydroxy-3-methylbenzaldehyde in accordance with the
method disclosed in, for example, Organic Synthesis, Collective
Volume, vol. 4, pp. 836-838 (conversion of phenol into phenyl
methyl ether, methylation reaction), and The Journal of Organic
Chemistry, 1963, vol. 28, 1128 or Synthetic Communications, 1985,
vol. 15, No. 10, pp. 855-864 (conversion of carbonyl group into
olefin, Wittg reaction), and Organic Reactions, 1973, vol. 20, pp.
1-131 or Journal of the American Chemical Society, 1975, vol. 97,
p. 3428 or Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624
(construction of cyclopropyl group, Simmons-Smith reaction), and
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-Methoxy-6-methylphenol can be produced by the method disclosed
in, for example, Synthetic Communications, 1996, vol. 26, No. 1,
pp. 49-62 from commercially available
1,2-dimethoxy-3-methylbenzene.
2,6-Diethylphenol can be produced by the method disclosed in, for
example, Journal of Medicinal Chemistry, 1960, vol. 2, pp.
201-212.
2-Cyclopropyl-6-ethylphenol can be produced from commercially
available 2-ethylphenol in accordance with the method disclosed in,
for example, Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and Helvetica Chimica Acta, 1992,
vol. 75, p. 457 (conversion of phenol into phenylmethoxymethyl
ether, methoxymethylation reaction), and Tetrahedron Letters, 2000,
vol. 41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction), and Tetrahedron, 1998, vol. 54,
pp. 15861-15869 (conversion of phenylmethoxymethyl ether into
phenol, demethoxymethylation reaction).
2,6-Dipropylphenol can be produced by the method disclosed in, for
example, Liebigs Annalen der Chemie, 1919, vol. 418, pp. 90-91
(synthesis of 2,6-diallylphenol), and Bulletin de la Societe
Chemique de France, 1937, vol. 5, No. 4, pp. 1080-1083 (conversion
of allyl group into propyl group, hydrogenation reaction).
3-Cyclopropyl-6-isopropylphenol can be produced in accordance with
the method disclosed in, for example, Journal of the Chemical
Society: Parkin transaction I, 1980, pp. 1862-1865 (synthesis of
2-hydroxy-3-isopropylbenzaldehyde), and Organic Synthesis,
Collective Volume, vol. 4, pp. 836-838 (conversion of phenol into
phenyl methyl ether, methylation reaction), and the method
disclosed in The Journal of Organic Chemistry, 1963, vol. 28, p.
1128 or Synthetic Communications, 1985, vol. 15, No. 10, pp.
855-864 (conversion of carbonyl group into olefin, Wittg reaction),
and the method disclosed in Organic Reactions, 1973, vol. 20, pp.
1-131 or Journal of the American Chemical Society, 1975, vol. 97,
p. 3428 or Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624
(construction of cyclopropyl group, Simmons-Smith reaction), and
the method disclosed in Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
3-tert-Butyl-6-cyclopropylphenol can be produced in accordance with
the method disclosed in, for example, commercially available
3-tert-butyl-2-hydroxybenzaldehyde , Organic Synthesis, Collective
Volume, vol. 4, pp. 836-838 (conversion of phenol into phenyl
methyl ether, methylation reaction), and the method disclosed in
The Journal of Organic Chemistry, 1963, vol. 28, p. 1128 or
Synthetic Communications, 1985, vol. 15, No. 10, pp. 855-864
(conversion of carbonyl group into olefin, Wittg reaction), and the
method disclosed in Organic Reactions, 1973, vol. 20, pp. 1-131 or
Journal of the American Chemical Society, 1975, vol. 97, p. 3428 or
Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624 (construction of
cyclopropyl group, Simmons-Smith reaction), and the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2,6-Dicyclopropylphenol can be produced in accordance with the
method disclosed in, for example, Tetrahedron Letters, 1997, vol.
38, No. 17, pp. 3111-3114 (synthesis of
2-hydroxyisophthalaldehyde), and the method disclosed in Organic
Synthesis, Collective Volume, vol. 4, pp. 836-838 (conversion of
phenol into phenyl methyl ether, methylation reaction), and the
method disclosed in The Journal of Organic Chemistry, 1963, vol.
28, p. 1128 or Synthetic Communications, 1985, vol. 15, No. 10, pp.
855-864 (conversion of carbonyl group into olefin, Wittg reaction),
and the method disclosed in Organic Reactions, 1973, vol. 20, pp.
1-131 or Journal of the American Chemical Society, 1975, vol. 97,
p. 3428 or Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624
(construction of cyclopropyl group, Simmons-Smith reaction), and
the method disclosed in Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
2-Cyclopropyl-6-methoxyphenol can be produced from commercially
available 2-hydroxy-3-methoxybenzaldehyde in accordance with the
method disclosed in, for example, Helvetica Chimica Acta, 1992,
vol. 75, p. 457 (conversion of phenol into phenylmethoxymethyl
ether, methoxymethylation reaction), and The Journal of Organic
Chemistry, 1963, vol. 28, p. 1128 or Synthetic Communications,
1985, vol. 15, No. 10, pp. 855-864 (conversion of carbonyl group
into olefin, Wittg reaction), and the method disclosed in Organic
Reactions, 1973, vol. 20, pp. 1-131 or Journal of the American
Chemical Society, 1975, vol. 97, p. 3428 or Tetrahedron Letters,
1998, vol. 39, pp. 8621-8624 (construction of cyclopropyl group,
Simmons-Smith reaction), and the method disclosed in Tetrahedron,
1998, vol. 54, pp. 15861-15869 (conversion of phenylmethoxymethyl
ether into phenol, demethoxymethylation reaction).
2-Cyclopropyl-6-ethoxyphenol can be produced from commercially
available 3-ethoxy-2-hydroxybenzaldehyde in accordance with the
method disclosed in, for example, Organic Synthesis, Collective
Volume, vol. 4, pp. 836-838 (conversion of phenol into phenyl
methyl ether, methylation reaction), and the method disclosed in
The Journal of Organic Chemistry, 1963, vol. 28, p. 1128 or
Synthetic Communications, 1985, vol. 15, No. 10, pp. 855-864
(conversion of carbonyl group into olefin, Wittg reaction), and the
method disclosed in Organic Reactions, 1973, vol. 20, pp. 1-131 or
Journal of the American Chemical Society, 1975, vol. 97, p. 3428 or
Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624 (construction of
cyclopropyl group, Simmons-Smith reaction), and the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2,6-Di[(1E)-1-propenyl]phenol can be produced by the method
disclosed in, for example, Liebigs Annalen der Chemie, 1919, vol.
418, pp. 90-91 (synthesis of 2,6-diallylphenol), and the method
disclosed in Journal of the American Chemical Society, 1956, vol.
78, pp. 1709-1713(isomerization reaction).
2,6-Diallylphenol can be produced by the method disclosed in, for
example, Liebigs Annalen der Chemie, 1919, vol. 418, pp. 90-91.
3,5-Diisopropylphenol can be produced by the method disclosed in,
for example, U.S. Patent (U.S. Pat. No. 2,790,010).
2-Bromo-3,5-dimethylphenol can be produced in accordance with the
method disclosed in, Bulletin of the Chemical Society of Japan,
1993, vol. 66, p. 1576 (brominetion reaction of phenol) from
commercially available 3,5-dimethylphenol.
3,5-Dimethyl-2-propylphenol can be produced by the method disclosed
in, for example, Bulletin of the Chemical Society of Japan, 1968,
vol. 41, No. 3, pp. 745-746.
2-Cyclopropyl-3,5-dimethylphenol can be produced from commercially
available 3,5-dimethylphenol in accordance with the method
disclosed in, for example, Tetrahedron, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and Organic Synthesis, Collective
Volume vol. 4, pp. 836-838 (conversion of phenol into phenyl methyl
ether, methylation reaction), and the method disclosed in
Tetrahedron Letters, 1979, vol. 20, pp. 4159-4162 or the method
disclosed in Tetrahedron, 1997, vol. 53, No. 43, pp. 14599-14614 or
the method disclosed in Bulletin of the Chemical Society of Japan,
1971, vol. 44, pp. 2237-2248 (conversion reaction of aromatic
bromide into aromatic aldehyde), and the method disclosed in The
Journal of Organic Chemistry, 1963, vol. 28, p. 1128 or Synthetic
Communications, 1985, vol. 15, No. 10, pp. 855-864 (conversion of
carbonyl group into olefin, Wittg reaction), and the method
disclosed in Organic Reactions, 1973, vol. 20, pp. 1-131 or Journal
of the American Chemical Society, 1975, vol. 97, p. 3428 or
Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624 (construction of
cyclopropyl group, Simmons-Smith reaction), and the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
3,5-Dimethyl-2-(methylsulfanyl)phenol can be produced by the method
disclosed in, for example, Tetrahedron Letters, 1999, vol. 40, No.
35, pp. 6357-6358.
2-Bromo-3,6-dimethylphenol can be produced in accordance with the
method disclosed in, for example, Tetrahedron Letters, 1998, vol.
39, p. 2947 (bromination reaction of phenol) from commercially
available 3,6-dimethylphenol.
6-Bromo-3-fluoro-2-methylphenol can be produced, from
3-fluoro-2-methylphenol which can be produced from commercially
available 3-fluoro-2-methylbenzaldehyde in accordance with the
method disclosed in Journal of the Chemical Society: Parkin
transaction I, 1974, p. 1353, in accordance with the method
disclosed in, for example, Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol).
6-Bromo-3-chloro-2-methylphenol can be produced in accordance with
the method disclosed in Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol) from 3-chloro-2-methylphenol which
can be produced from commercially available
1-chloro-3-methoxy-2-methylbenzene in accordance with the method
disclosed in Organic Synthesis, Collective Volume, vol. 5, pp.
412-414 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
3-Chloro-6-cyclopropyl-2-methylphenol can be produced from
3-chloro-2-methylphenol which can be produced from commercially
available 1-chloro-3-methoxy-2-methylbenzene in accordance with the
method disclosed in Organic Synthesis, Collective Volume, vol. 5,
pp. 412-414 (conversion of phenylmethyl ether into phenol,
demethylation reaction), in accordance with the method disclosed in
Tetrahedron Letters, 1998, vol. 39, p. 2947. (bromination reaction
of phenol) and Helvetica Chimica Acta, 1992, vol. 75, p. 457
(conversion of phenol into phenylmethoxymethyl ether,
methoxymethylation reaction), and Tetrahedron Letters, 2000, vol.
41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction), and Tetrahedron, 1998, vol. 54,
pp. 15861-15869 (conversion of phenylmethoxymethyl ether into
phenol, demethoxymethylation reaction).
6-Bromo-2,3-dimethylphenol can be produced in accordance with the
method disclosed in, for example, Tetrahedron Letters, 1998, vol.
39, p. 2947 (bromination reaction of phenol) from commercially
available 2,3-dimethylphenol.
6-Cyclopropyl-2,3-dimethylphenol can be produced from commercially
available 2,3-dimethylphenol in accordance with the method
disclosed in, for example, Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol), and Helvetica Chimica Acta,
1992, vol. 75, p. 457 (conversion of phenol into
phenylmethoxymethyl ether, methoxymethylation reaction), and
Tetrahedron Letters, 2000, vol. 41, pp. 4251-4255 (construction of
cyclopropyl group, Suzuki-Miyaura coupling reaction), and
Tetrahedron, 1998, vol. 54, pp. 15861-15869 (conversion of
phenylmethoxymethyl ether into phenol, demethoxymethylation
reaction).
2-Hydroxy-3,4-dimethylbenzaldehyde O-methyloxime can be produced
from commercially available 2,3-dimethylphenol in accordance with
the method disclosed in, for example, Tetrahedron Letters, 1998,
vol. 39, p. 2947 (bromination reaction of phenol), and Helvetica
Chimica Acta, 1992, vol. 75, p. 457 (conversion of phenol into
phenylmethoxymethyl ether, methoxymethylation reaction), and the
method disclosed in Tetrahedron Letters, 1979, vol. 20, pp.
4159-4162 or the method disclosed in Tetrahedron, 1997, vol. 53,
No. 43, pp. 14599-14614 or the method disclosed in Bulletin of the
Chemical Society of Japan, 1971, vol. 44, pp. 2237-2248 (conversion
reaction of aromatic bromide into aromatic aldehyde), and the
method disclosed in Journal of the Chemical Society: Perkin
transactions I, 1979, pp. 643-645 (oximation reaction), and
Tetrahedron, 1998, vol. 54, pp. 15861-15869 (conversion of
phenylmethoxymethyl ether into phenol, demethoxymethylation
reaction).
6-Methoxy-2,3-dimethylphenol can be produced from commercially
available 3,4-dimethylphenol in accordance with the method
disclosed in, for example, Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol) and the method disclosed in
Tetrahedron Letters, 1979, vol. 20, pp. 4159-4162 or the method
disclosed in Tetrahedron, 1997, vol. 53, No. 43, pp. 14599-14614 or
the method disclosed in Bulletin of the Chemical Society of Japan,
1971, vol. 44, pp. 2237-2248 (conversion reaction of aromatic
bromide into aromatic aldehyde), and the method disclosed in
Journal of the Chemical Society: Parkin transaction I, 1974, p.
1353.
6-Bromo-3-methoxy-2-methylphenol can be produced in accordance with
the method disclosed in, Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol) from 3-methoxy-2-methylphenol
which can be produced from commercially available
2-methyl-1,3-benzene diol in accordance with the method disclosed
in Organic Synthesis, Collective Volume, vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction).
6-Cyclopropyl-3-methoxy-2-methylphenol can be produced from
3-methoxy-2-methylphenol which can be produced from commercially
available 2-methyl-1,3-benzene diol in accordance with the method
disclosed in Organic Synthesis, Collective Volume, vol. 4, pp.
836-838 (conversion of phenol into phenyl methyl ether, methylation
reaction), in accordance with the method disclosed in Tetrahedron
Letters, 1998, vol. 39, p. 2947 (bromination reaction of phenol),
and the method disclosed in Helvetica Chimica Acta, 1992, vol. 75,
p. 457 (conversion of phenol into phenylmethoxymethyl ether,
methoxymethylation reaction), and the method disclosed in
Tetrahedron Letters, 2000, vol. 41, pp. 4251-4255 (construction of
cyclopropyl group, Suzuki-Miyaura coupling reaction), and the
method disclosed in Tetrahedron, 1998, vol. 54, pp. 15861-15869
(conversion of phenylmethoxymethyl ether into phenol,
demethoxymethylation reaction).
2-Cyclopropyl-3,6-dimethylphenol can be produced from commercially
available 2,5-dimethylphenol in accordance with the method
disclosed in, for example, Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol), and the method disclosed in
Organic Synthesis, Collective Volume, vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction), and the method disclosed in Tetrahedron Letters, 1979,
vol. 20, pp. 4159-4162 or the method disclosed in Tetrahedron,
1997, vol. 53, No. 43, pp. 14599-14614 or the method disclosed in
Bulletin of the Chemical Society of Japan, 1971, vol. 44, pp.
2237-2248 (conversion reaction of aromatic bromide into aromatic
aldehyde), and the method disclosed in The Journal of Organic
Chemistry, 1963, vol. 28, p. 1128 or Synthetic Communications,
1985, vol. 15, No. 10, pp. 855-864 (conversion of carbonyl group
into olefin, Wittg reaction), and the method disclosed in Organic
Reactions, 1973, vol. 20, pp. 1-131 or Journal of the American
Chemical Society, 1975, vol. 97, p. 3428 or Tetrahedron Letters,
1998, vol. 39, pp. 8621-8624 (construction of cyclopropyl group,
Simmons-Smith reaction), and the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
2-Allyl-6-ethyl-3-methoxyphenol can be produced from
2-ethyl-5-methoxyphenol which can be produced in accordance with
the method disclosed in Chemical and Pharmaceutical Bulletin, 1979,
vol. 27, No. 6, pp. 1490-1494, in accordance with the method
disclosed in, for example, Organic Reactions, 1949, vol. 2, pp.
1-48 (allylation reaction of phenol, Claisen transition).
3,6-Dimethyl-2-[(methylsulfanyl)methyl]phenol can be produced by
the method disclosed in, for example, Journal of the American
Chemical Society, 1966, vol. 88, No. 24, pp. 5855-5864.
5-Bromo-4-indanol can be produced in accordance with the method
disclosed in, for example, Journal of the American Chemical
Society, 1946, vol. 68, p. 2487 (reduction of carbonyl group,
Wolff-Kishner Reduction), and Tetrahedron Letters, 1998, vol. 39,
p. 2947 (bromination reaction of phenol) from commercially
available 4-hydroxy-1-indanone.
5-Methyl-4-indanol can be produced from commercially available
4-hydroxy-1-indanone in accordance with the method disclosed in,
for example, Journal of the American Chemical Society, 1946, vol.
68, p. 2487 (reduction of carbonyl group, Wolff-Kishner Reduction),
and the method disclosed in Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol), and the method disclosed in
Helvetica Chimica Acta, 1990, vol. 75, p. 457 (conversion of phenol
into phenylmethoxymethyl ether, methoxymethylation reaction), and
the method disclosed in Helvetica Chimica Acta, 1990, vol. 73, pp.
417-425 (conversion reaction of bromo group into methyl group), and
the method disclosed in Tetrahedron, 1998, vol. 54, pp. 15861-15869
(conversion of phenylmethoxymethyl ether into phenol,
demethoxymethylation reaction).
5-Ethyl-4-indanol can be produced from commercially available
4-hydroxy-1-indanone in accordance with the method disclosed in,
for example, Journal of the American Chemical Society, 1946, vol.
68, p. 2487 (reduction of carbonyl group, Wolff-Kishner Reduction),
and the method disclosed in Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol), and the method disclosed in
Helvetica Chimica Acta, 1992, vol. 75, p. 457 (conversion of phenol
into phenylmethoxymethyl ether, methoxymethylation reaction), and
the method disclosed in Helvetica Chimica Acta, 1990, vol. 73, pp.
417-425 (conversion reaction of bromo group into ethyl group), and
the method disclosed in Tetrahedron, 1998, vol. 54, pp. 15861-15869
(conversion of phenylmethoxymethyl ether into phenol,
demethoxymethylation reaction).
5-Cyclopropyl-4-indanol can be produced from commercially available
4-hydroxy-1-indanone in accordance with the method disclosed in,
for example, Journal of the American Chemical Society, 1946, vol.
68, p. 2487 (reduction of carbonyl group, Wolff-Kishner Reduction),
and the method disclosed in Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol) and the method disclosed in
Organic Synthesis, Collective Volume, vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction), and Tetrahedron Letters, 2000, vol. 41, pp. 4251-4255
(construction of cyclopropyl group, Suzuki-Miyaura coupling
reaction), and the method disclosed in Bioscience, Biotechnology,
and Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
6-Methyl-2,3-dihydro-1-benzofuran-7-ol can be produced in
accordance with the method disclosed in, for example, Journal of
the Chemical Society, 1948, p. 894 (reduction of olefin) from
6-methyl-1-benzofuran-7-ol. 6-Methyl-1-benzofuran-7-ol can be
produced, for example, from 2-methoxy-3-methylphenol which can be
produced by the method disclosed in Tetrahedron Letters, 1998, vol.
39, p. 2947, in accordance with the method disclosed in Journal of
the Chemical Society: Perkin transactions I, 1988, p. 3029
(construction of benzofuran ring), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
6-Bromo-1-benzofuran-7-ol can be produced from commercially
available 7-methoxy-1-benzofuran in accordance with the method
disclosed in, for example, Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction), and
Tetrahedron Letters, 1998, vol. 39, p. 2947 (bromination reaction
of phenol).
6-Methyl-1-benzofuran-7-ol can be produced from
2-methoxy-3-methylphenol which can be produced by the method
disclosed in Tetrahedron Letters, 1998, vol. 39, p. 2947, in
accordance with the method disclosed in, for example, Journal of
the Chemical Society: Perkin transactions I, 1988, p. 3029
(construction of benzofuran ring), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
6-Cyclopropyl-1-benzofuran-7-ol can be produced from commercially
available 7-methoxy-1-benzofuran in accordance with the method
disclosed in, for example, Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction), and the
method disclosed in Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and the method disclosed in
Helvetica Chimica Acta, 1992, vol. 75, p. 457 (conversion of phenol
into phenylmethoxymethyl ether, methoxymethylation reaction), and
the method disclosed in Tetrahedron Letters, 2000, vol. 41, pp.
4251-4255 (construction of cyclopropyl group, Suzuki-Miyaura
coupling reaction), and the method disclosed in Tetrahedron, 1998,
vol. 54, pp. 15861-15869 (conversion of phenylmethoxymethyl ether
into phenol, demethoxymethylation reaction).
2,4-Dicyclopropyl-6-fluorophenol can be produced from commercially
available 2-fluorophenol in accordance with the method disclosed
in, for example, Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and Helvetica Chimica Acta, 1992,
vol. 75, p. 457 (conversion of phenol into phenylmethoxymethyl
ether, methoxymethylation reaction), and Tetrahedron Letters, 2000,
vol. 41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction), and the method disclosed in
Tetrahedron, 1998, vol. 54, pp. 15861-15869 (conversion of
phenylmethoxymethyl ether into phenol, demethoxymethylation
reaction).
2,4-Dibromo-3,6-dimethylphenol can be produced in accordance with
the method disclosed in, for example, Tetrahedron Letters, 1998,
vol. 39, p. 2947 (bromination reaction of phenol) from commercially
available 3,6-dimethylphenol.
2-Bromo-4,6-dimethylphenol can be produced in accordance with the
method disclosed in, for example, Tetrahedron Letters, 1998, vol.
39, p. 2947 (bromination reaction of phenol) from commercially
available 2,4-dimethylphenol.
2-Ethyl-4,6-diiodophenol can be produced in accordance with the
method disclosed in, Australian Journal of Chemistry, 1997, vol.
50, No. 7, pp. 767-770 (iodation reaction of phenol) from
commercially available 2-ethylphenol.
2-Cyclopropyl-4,6-dimethylphenol can be produced from commercially
available 2,4-dimethylphenol in accordance with the method
disclosed in, for example, Tetrahedron Letters, 1998, vol. 39, p.
2947 (bromination reaction of phenol), and the method disclosed in
Helvetica Chimica Acta, 1992, vol. 75, p. 457 (conversion of phenol
into phenylmethoxymethyl ether, methoxymethylation reaction), and
the method disclosed in Tetrahedron Letters, 2000, vol. 41, pp.
4251-4255 (construction of cyclopropyl group, Suzuki-Miyaura
coupling reaction), and the method disclosed in Tetrahedron, 1998,
vol. 54, pp. 15861-15869 (conversion of phenylmethoxymethyl ether
into phenol, demethoxymethylation reaction).
2-Bromo-3,5,6-trimethylphenol can be produced in accordance with
the method disclosed in, for example, Tetrahedron Letters, 1998,
vol. 39, p. 2947 (bromination reaction of phenol) from commercially
available 2,3,5-trimethylphenol.
5,6-Dimethyl-4-indanol can be produced from commercially available
7-methyl-2H-chromen-2-one in accordance with the method disclosed
in, for example, Nihon Kagakukaishi (Journal of Japan Chemical
Association), 1974, pp. 136-146, and the method disclosed in
Organic Reactions, 1941, vol. 1, p. 155 (Clemmensen reduction).
1,2,3,5,6,7-Hexahydro-s-indacen-4-ol can be produced from
commercially available indane by the method disclosed in, for
example, Journal of the American Chemical Society, 1977, vol. 99,
pp. 8007-8014, and the method disclosed in Organic Reactions, 1941,
vol. 1, p. 155 (Clemmensen reduction), and the method disclosed in
The Journal of Organic Chemistry, 1977, vol. 42, pp. 3260-3264.
3-(1,3-Dioxolan-2-yl)phenol can be produced in accordance with the
method disclosed in, for example, Tetrahedron Letters, 1989, vol.
30, No. 13, pp. 1609-1612 from 3-hydroxybenzaldehyde.
3'-(Trifluoromethyl)[1,1'-biphenyl]-3-ol can be produced in
accordance with the method disclosed in, for example, Chemical
Reviews, 1995, vol. 95, pp. 2457-2483 (phenylation reaction,
Suzuki-Miyaura coupling reaction) from commercially available
3-iodophenol and 3-(trifluoromethyl)phenylboronic acid.
3-Hydroxy-4-methylbenzonitrile can be produced by the method
disclosed in, for example, Monatshefte fur Chemie, 1957, vol. 88,
pp. 228, 230.
Ethyl 3-hydroxy-4-methylbenzoate can be produced by the method
disclosed in, for example, The Journal of Organic Chemistry, 1961,
vol. 26, pp. 1732-1734.
3-Hydroxy-4-methylbenzamide can be produced in accordance with the
method disclosed in, for example, Phosphorus and Sulfur, 1980, vol.
9, pp. 155-164 from commercially available
3-hydroxy-4-methylbenzoic acid.
3,6-Dimethyl-2-propylphenol can be produced by the method disclosed
in, for example, Journal of Polymer Science, 1948, vol. 3, p. 448,
p. 452.
2-Hydroxy-3,4,6-trimethylbenzaldehyde can be produced by the method
disclosed in, for example, Liebigs Annalen der Chemie, 1906, vol.
347, p. 379.
2-Hydroxy-3,4,6-trimethylbenzaldehyde O-methyloxime can be produced
in accordance with the method disclosed in, for example, Liebigs
Annalen der Chemie, 1906, vol. 347, p. 379 (synthesis of
2-hydroxy-3,4,6-trimethylbenzaldehyde), and in accordance with the
method disclosed in Chemical Pharmaceutical Bulletin, 1988, vol.
36, No. 8, pp. 3134-3137.
2-[1-(Methoxymethyl)cyclopropyl]phenol can be produced from
2-methoxy-1-(2-methoxyphenyl)ethanone which can be obtained by the
method disclosed in The Journal of Organic Chemistry, 1942, vol. 7,
pp. 444-456, in accordance with the method disclosed in, for
example, The Journal of Organic Chemistry, 1963, vol. 28, p. 1128
or Synthetic Communications, 1985, vol. 15, No. 10, pp. 855-864
(conversion of carbonyl group into olefin, Wittig reaction), and
the method disclosed in Organic Reactions, 1973, vol. 20, pp. 1-131
or Journal of the American Chemical Society, 1975, vol. 97, p. 3428
or Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624 (construction
of cyclopropyl group, Simmons-Smith reaction), and the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2-(1-Methoxycyclopropyl)phenol can be produced from
1-methoxy-2-(1-methoxyvinyl)benzene which can be produced by the
method disclosed in The Journal of Organic Chemistry, 1998, vol.
63, pp. 4632-4635, in accordance with the method disclosed in, for
example, Organic Reactions, 1973, vol. 20, pp. 1-131 or Journal of
the American Chemical Society, 1975, vol. 97, p. 3428 or
Tetrahedron Letters, 1998, vol. 39, pp. 8621-8624 (construction of
cyclopropyl group, Simmons-Smith reaction), and the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
2-(2-Hydroxyphenyl)cyclopropanecarbonitrile can be produced from
3-(2-methoxyphenyl)acrylonitrile which can be produced by the
method disclosed in Journal of Medicinal Chemistry, 1988, vol. 31,
No. 1, pp. 37-54, in accordance with the method disclosed in, for
example, Bioscience, Biotechnology, and Biochemistry, 1993, vol.
57, No. 9, pp. 1572-1574 or Japanese Provisional Patent Publication
No. 11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction), and the method disclosed in Helvetica
Chimica Acta, 1992, vol. 75, p. 457 (conversion of phenol into
phenylmethoxymethyl ether, methoxymethylation reaction), and the
method disclosed in The Journal of Organic Chemistry, 1973, vol.
38, pp. 1793-1797 or The Journal of Organic Chemistry, 1970, vol.
35, pp. 374-379 (cyclopropanation reaction), and the method
disclosed in Tetrahedron, 1998, vol. 54, pp. 15861-15869
(conversion of phenylmethoxymethyl ether into phenol,
demethoxymethylation reaction).
2-(2-Ethoxycyclopropyl)phenol can be produced in accordance with
the method disclosed in, for example, The Journal of Organic
Chemistry, 1981, vol. 46, pp. 5143-5147 (conversion of benzyl
alcohol into benzyl chloride), and the method disclosed in Journal
of the American Chemical Society, 1973, vol. 95, No. 2, pp. 581-582
(construction of cyclopropyl group), and the method disclosed in
Tetrahedron, 1998, vol. 54, pp. 15861-15869 (conversion of
phenylmethoxymethyl ether into phenol, demethoxymethylation
reaction) from [2-(methoxymethoxy)phenyl]methanol which can be
produced by the method disclosed in Heterocycles, 1998, vol. 48,
No. 7, pp. 1373-1394.
2-(2,2-Difluorocyclopropyl)phenol can be produced in accordance
with the method disclosed in, for example, The Journal of Organic
Chemistry, 1973, vol. 38, pp. 1793-1797 or The Journal of Organic
Chemistry, 1970, vol. 35, pp. 374-379 (cyclopropanization
reaction), and the method disclosed in Organic Synthesis,
Collective Volume, vol. 5, pp. 412-414 (conversion of phenylmethyl
ether into phenol, demethylation reaction) from
1-(2,2-difluorovinyl)-2-methoxybenzene which can be produced by the
method disclosed in Bulletin de la Societe Chemique de France,
1995, pp. 850-856.
2-(2,2-Dichlorocyclopropyl)phenol can be produced in accordance
with the method disclosed in, for example, The Journal of Organic
Chemistry, 1963, vol. 28, p. 1128 or Synthetic Communications,
1985, vol. 15, No. 10, pp. 855-864 (conversion of carbonyl group
into olefin, Wittig reaction), and the method disclosed in
Synthetic Communications, 1999, vol. 29, No. 23, pp. 4101-4112
(conversion of olefin into dichlorocyclopropane), and the method
disclosed in Tetrahedron, 1998, vol. 54, pp. 15861-15869
(conversion of phenylmethoxymethyl ether into phenol,
demethoxymethylation reaction) from 2-(methoxymethoxy)benzaldehyde
which can be produced by the method disclosed in Heterocycles,
1998, vol. 48, No. 7, pp. 1373-1394.
2-(2,2-Dibromocyclopropyl)phenol can be produced in accordance with
the method disclosed in, for example, from commercially available
1-methoxy-2-vinylbenzene, Synthetic Communications, 1999, vol. 29,
No. 23, pp. 4101-4112 (using bromoform in place of chloroform.
Conversion of olefin into dibromocyclopropane), and the method
disclosed in Organic Synthesis, Collective Volume, vol. 5, pp.
412-414 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-Isopropenylphenol can be produced in accordance with the method
disclosed in, for example, from commercially available
1-(2-methoxyphenyl)ethanone, The Journal of Organic Chemistry,
1963, vol. 28, p. 1128 or Synthetic Communications, 1985, vol. 15,
No. 10, pp. 855-864 (conversion of carbonyl group into olefin,
Wittig reaction), and the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction).
3-(2-Hydroxyphenyl)acrylonitrile can be produced in accordance with
the method disclosed in, for example, Bioscience, Biotechnology,
and Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction) from
3-(2-methoxyphenyl)acrylonitrile which can be produced by the
method disclosed in Journal of Medicinal Chemistry, 1988, vol. 31,
No. 1, pp. 37-54.
2-Ethynylphenol can be produced by the method disclosed in, for
example, Canadian Journal of Chemistry, 1997, vol. 75, No. 9, pp.
1256-1263 from commercially available 1-benzofuran.
Bicyclo[4.2.0]octa-1,3,5-trien-2-ol can be produced in accordance
with the method disclosed in, for example, Organic Reactions, 1941,
vol. 1, p. 155 (Clemmensen reduction), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 or Organic Synthesis, Collective Volume, vol. 5, pp.
412-414 (conversion of phenylmethyl ether into phenol,
demethylation reaction) from
5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-one which can be produced
by the method disclosed in The Journal of Organic Chemistry, 1982,
vol. 47, pp. 2393-2396.
2-Bromo-6-chlorophenol can be produced in accordance with the
method disclosed in, for example, Tetrahedron Letters, 1998, vol.
39, p. 2947 (bromination reaction of phenol) from commercially
available 2-chlorophenol.
3-Bromo-2-hydroxybenzonitrile can be produced in accordance with
the method disclosed in, for example, Tetrahedron Letters, 1998,
vol. 39, p. 2947 (bromination reaction of phenol) from commercially
available 2-hydroxybenzonitrile.
2-(2,2-Dichlorocyclopropyl)-6-methylphenol can be produced in
accordance with the method disclosed in, for example, from
commercially available 2-hydroxy-3-methylbenzaldehyde, Organic
Synthesis, Collective Volume, vol. 4, pp. 836-838 (conversion of
phenol into phenyl methyl ether, methylation reaction), and the
method disclosed in The Journal of Organic Chemistry, 1963, vol.
28, p. 1128 or Synthetic Communications, 1985, vol. 15, No. 10, pp.
855-864 (conversion of carbonyl group into olefin, Wittig
reaction), and the method disclosed in Synthetic Communications,
1999, vol. 29, No. 23, pp. 4101-4112 (conversion of olefin into
dichlorocyclopropane), and the method disclosed in Organic
Synthesis, Collective Volume, vol. 5, pp. 412-414 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
2-Methyl-6-vinylphenol can be produced in accordance with the
method disclosed in, for example, for example, from commercially
available 2-hydroxy-3-methylbenzaldehyde, Organic Synthesis,
Collective Volume, vol. 4, pp. 836-838 (conversion of phenol into
phenyl methyl ether, methylation reaction), and the method
disclosed in The Journal of Organic Chemistry, 1963, vol. 28, p.
1128 or Synthetic Communications, 1985, vol. 15, No. 10, pp.
855-864 (conversion of carbonyl group into olefin, Wittig
reaction), and the method disclosed in Bioscience, Biotechnology,
and Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
6-Cyclopropyl-3-fluoro-2-methylphenol can be produced in accordance
with the method disclosed in, for example, from commercially
available 3-fluoro-2-methylbenzaldehyde, The Journal of Organic
Chemistry, 1999, vol. 64, pp. 7921-7928 or Journal of the Chemical
Society: Parkin transaction I) 1974, p. 1353 (Baeyer-Villiger
oxidation, convertion of an aromatic aldehyde into phenol), and the
method disclosed in Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and the method disclosed in
Organic Synthesis, Collective Volume, vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction) and the method disclosed in Tetrahedron Letters, 2000,
vol. 41, pp. 4251-4255 (construction of cyclopropyl group,
Suzuki-Miyaura coupling reaction), and the method disclosed in
Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No. 9,
pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
5-Methyl-1-benzofuran-4-ol can be produced from methyl
4-hydroxy-1-benzofuran-5-carboxylate which can be produced by the
method disclosed in Tetrahedron, 1995, vol. 51, pp. 4009-4022, in
accordance with the method disclosed in, for example, Organic
Synthesis, Collective Volume, vol. 4, pp. 836-838 (conversion of
phenol into phenyl methyl ether, methylation reaction), and the
method disclosed in The Journal of Organic Chemistry, 2001, vol.
66, pp. 4965-4972 (reduction of ester to alcohol), and the method
disclosed in Journal of Medicinal Chemistry, 1999, vol. 42, No. 6,
pp. 1007-1017 (conversion of benzyl alcohol into
benzylmethanesulfonyl ester), and the method disclosed in The
Journal of Organic Chemistry, 1969, vol. 34, p. 3923 or Synthetic
Communications, 2001, vol. 31, No. 9, pp. 1373-1382 (reduction of
halogen compound, tosylate, and mesylate), and the method disclosed
in Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, No.
9, pp. 1572-1574 or Japanese Provisional Patent Publication No.
11-322755 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-(2-Chloro-2-fluorocyclopropyl)phenol can be produced from
2-(methoxymethoxy)benzaldehyde which can be produced by the method
disclosed in Heterocycles, 1998, vol. 48, No. 7, pp. 1373-1394, in
accordance with the method disclosed in, for example, Journal of
Fluorine Chemistry, 1983, vol. 23, pp. 339-357 (conversion of
carbonyl group into chlorofluoroolefin), and the method disclosed
in The Journal of Organic Chemistry, 1973, vol. 38, pp. 1793-1797
or The Journal of Organic Chemistry, 1970, vol. 35, pp. 374-379
(cyclopropanation reaction), and the method disclosed in Organic
Synthesis, Collective Volume, vol. 5, pp. 412-414 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
3-(Benzyloxy)phenol can be produced by the method disclosed in, for
example, The Journal of Organic Chemistry, 1997, vol. 62, No. 10,
pp. 3062-3075.
1-Methyl-1H-indol-4-ol can be produced in accordance with the
method disclosed in, for example, Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction) from
commercially available 4-methoxy-1-methyl-1H-indole.
1-Methyl-1H-indol-7-ol can be produced in accordance with the
method disclosed in, for example, Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction) from
7-methoxy-1-methyl-1H-indole which can be produced by the method
disclosed in Journal of Medicinal Chemistry, 1992, vol. 35, No. 1,
pp. 177-184.
1-(4-Hydroxy-3-methylphenyl)ethanone O-methyloxime can be produced
in accordance with the method disclosed in, for example, Journal of
the American Chemical Society, 1986, vol. 108, pp. 6016-6023 from
commercially available 1-(4-hydroxy-3-methylphenyl)ethanone.
2-Isopropenyl-6-methylphenol can be produced from
1-(2-hydroxy-3-methylphenyl)ethanone which can be produced by the
method disclosed in Chemische Berichte, 1925, vol. 58, p. 41, in
accordance with the method disclosed in, for example, Organic
Synthesis, Collective Volume, vol. 4, pp. 836-838 (conversion of
phenol into phenyl methyl ether, methylation reaction), and the
method disclosed in The Journal of Organic Chemistry, 1963, vol.
28, p. 1128 or Synthetic Communications, 1985, vol. 15, No. 10, pp.
855-864 (conversion of carbonyl group into olefin, Wittig
reaction), and the method disclosed in Bioscience, Biotechnology,
and Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
1,1-Dimethyl-5-indanol can be produced in accordance with the
method disclosed in, for example, Organic Synthesis, Collective
Volume, vol. 5, pp. 412-414 (conversion of phenylmethyl ether into
phenol, demethylation reaction) from 5-methoxy-1,1-dimethylindane
which can be produced by the method disclosed in Bulletin of the
Chemical Society of Japan, 2000, vol. 73, No. 12, pp.
2779-2782.
3-Bromo-6-cyclopropyl-2-methylphenol can be produced from
commercially available 2-methyl-3-nitrophenol, in accordance with
the method disclosed in Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and the method disclosed in
Organic Synthesis, Collective Volume, vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction), and the modified method of the method disclosed in
Organic Synthesis, Collective Volume, vol. 1, pp. 445-447
(reduction of nitrophenol to aniline; 8.5 equivalents of zinc
powder and 25 equivalents of ammonium chloride are used based on
nitrophenol, reaction is carried out at room temperature), and the
method disclosed in Tetrahedron Letters, 2000, vol. 41, pp.
4251-4255 (construction of cyclopropyl group, Suzuki-Miyaura
coupling reaction), and the method disclosed in Organic Synthesis,
Collective Volume, vol. 3, pp. 185-187 or the method disclosed in
The Journal of Organic Chemistry, 1977, vol. 42, pp. 2426-2430
(conversion of anilines into bromobenzene, Sandmeyer reaction,
etc.) and the method disclosed in Bioscience, Biotechnology, and
Biochemistry, 1993, vol. 57, No. 9, pp. 1572-1574 or Japanese
Provisional Patent Publication No. 11-322755 (conversion of
phenylmethyl ether into phenol, demethylation reaction).
6-Cyclopropyl-2-methyl-3-nitrophenol can be produced from
commercially available 2-methyl-3-nitrophenol, in accordance with
the method disclosed in Tetrahedron Letters, 1998, vol. 39, p. 2947
(bromination reaction of phenol), and the method disclosed in
Organic Synthesis, Collective Volume, vol. 4, pp. 836-838
(conversion of phenol into phenyl methyl ether, methylation
reaction), and the modified method of the method disclosed in
Organic Synthesis, Collective Volume, vol. 1, pp. 445-447
(reduction of nitrophenol to aniline; 8.5 equivalents of zinc
powder and 25 equivalents of ammonium chloride are used based on
nitrophenol, reaction is carried out at room temperature), and the
method disclosed in Tetrahedron Letters, 2000, vol. 41, pp.
4251-4255 (construction of cyclopropyl group, Suzuki-Miyaura
coupling reaction), and the method disclosed in Bioscience,
Biotechnology, and Biochemistry, 1993, vol. 57, No. 9, pp.
1572-1574 or Japanese Provisional Patent Publication No. 11-322755
(conversion of phenylmethyl ether into phenol, demethylation
reaction), and the method disclosed in Tetrahedron, 1987, vol. 43,
No. 8, pp. 1753-1758 (conversion of aniline derivative into
nitrobenzene).
5-Methyl-1,3-dihydro-2-benzofuran-4-ol can be produced in
accordance with the method disclosed in, for example, Journal of
the American Chemical Society, 2000, vol. 122, pp. 11553-11554.
2-Fluoro-3,5,6-trimethylphenol can be produced from
2,3,5-trimethyl-6-nitrophenol which can be produced by the method
disclosed in Chemische Berichte, 1922, vol. 55, p. 2384, in
accordance with the method disclosed in, for example, Organic
Synthesis, Collective Volume, vol. 4, pp. 836-838 (conversion of
phenol into phenyl methyl ether, methylation reaction), and the
method disclosed in Liebigs Annalen der Chemie, 1957, vol. 608, p.
128, or the method disclosed in Organic Synthesis, Collective
Volume, vol. 5, 829-833 (Reduction of a nitro group into an amino
group), and the method disclosed in Synthesis, 1989, pp. 905-908
(conversion of aromatic amine into aromatic fluoride), and the
method disclosed in Organic Synthesis, Collective Volume, vol. 5,
pp. 412-414 (conversion of phenylmethyl ether into phenol,
demethylation reaction).
2-Chloro-3,5,6-trimethylphenol can be produced in accordance with
the method disclosed in, for example, Tetrahedron Letters, 1998,
vol. 39, p. 2947 (chlorication reaction of phenol; using
N-chlorosuccinimide in place of N-bromosuccinimide) from
commercially available 2,3,5-trimethylphenol.
2-Iodo-3,5,6-trimethylphenol can be produced in accordance with the
method disclosed in, for example, Tetrahedron Letters, 1998, vol.
39, p. 2947 (iodation reaction of phenol; using N-iodosuccinimide
in place of N-bromosuccinimide) from commercially available
2,3,5-trimethylphenol.
2-Ethyl-3,5,6-trimethylphenol can be produced in accordance with
the method disclosed in, for example, Journal of the American
Chemical Society, 1946, vol. 68, p. 2487 (reduction of carbonyl
group, Wolff-Kishner reduction) from
1-(2-hydroxy-3,4,6-trimethylphenyl)ethanone which can be produced
by the method disclosed in Chemical Research in Toxicology, 1997,
vol. 10, No. 3, pp. 335-343.
2-Isopropenyl-3,5,6-trimethylphenol can be produced from
1-(2-hydroxy-3,4,6-trimethylphenyl)ethanone which can be produced
by the method disclosed in Chemical Research in Toxicology, 1997,
vol. 10, No. 3, pp. 335-343, in accordance with the method
disclosed in, for example, Organic Synthesis, Collective Volume,
vol. 4, pp. 836-838 (conversion of phenol into phenyl methyl ether,
methylation reaction), and the method disclosed in The Journal of
Organic Chemistry, 1963, vol. 28, p. 1128 or Synthetic
Communications, 1985, vol. 15, No. 10, pp. 855-864 (conversion of
carbonyl group into olefin, Wittig reaction), and the method
disclosed in Bioscience, Biotechnology, and Biochemistry, 1993,
vol. 57, No. 9, pp. 1572-1574 or Japanese Provisional Patent
Publication No. 11-322755 (conversion of phenylmethyl ether into
phenol, demethylation reaction).
1-(2-Hydroxy-3,4,6-trimethylphenyl)ethanone can be produced by the
method disclosed in, for example, Chemical Research in Toxicology,
1997, vol. 10, No. 3, pp. 335-343.
2,3,5-Trimethyl-6-nitrophenol can be produced by the method
disclosed in, for example, Chemische Berichte, 1922, vol. 55, p.
2384.
2,4-Dichloro-3,5,6-trimethylphenol can be produced in accordance
with the method disclosed in, for example, Tetrahedron Letters,
1998, vol. 39, p. 2947 (chlorination reaction of phenol; using
N-chlorosuccinimide in place of N-bromosuccinimide) from
commercially available 2,3,5-trimethylphenol.
Pentamethylphenol can be produced by the method disclosed in, for
example, Journal of the Chemical Society, 1949, p. 624.
After completion of the above-mentioned respective reaction steps,
the objective compounds of the respective steps can be collected
from the reaction mixture according to the conventional manner. For
example, the reaction mixture is optionally neutralized, and also,
after removing insoluble materials by filtration when insoluble
materials exist, an organic solvent which is immiscible with water
is added to the mixture, and after washing with water, it can be
obtained by distillation of the solvent. The obtained desired
compound can be further purified according to the conventional
manner, if necessary, for example, recrystallization,
reprecipitation or chromatography, etc.
Compound (I) of the present invention can be made a salt. These
salts are included in the present invention so long as they can be
used as an agricultural and horticultural herbicide.
A salt of Compound (I) of the present invention may include, for
example, alkali metal salts such as lithium, sodium, potassium,
etc.; alkaline earth metal salts such as magnesium, calcium, etc.;
aluminum salts; transition metal salts such as iron, copper, etc.;
amine salts such as ammonium, trimethyl ammonium, triethyl
ammonium, tetramethyl ammonium, pyridinium, etc.; inorganic mineral
acid salts such as hydrochloride, sulfate, phosphate, etc.; or
organic acid salts such as formate, acetate, toluenesulfonate,
oxalate, etc.
When a pyridazine derivative is an acid component of the salt, the
salt can be produced by, for example, mixing the pyridazine
derivative and a base in the presence or absence of a solvent, and
removing the solvent.
The base to be used is not specifically limited so long as it is a
base generally showing a pH 8 or more, and for example, it may be
alkali metal hydroxides such as sodium hydroxide, potassium
hydroxide, etc.; alkali metal carbonates such as sodium carbonate,
potassium carbonate, cesium carbonate, etc.; metal alkoxides such
as sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.;
alkali metal salts of an organic acid such as sodium acetate,
potassium acetate, sodium formate, potassium formate, etc.; alkali
metal hydrides such as sodium hydride, potassium hydride, etc.;
alkali metals such as sodium, potassium, etc.; aliphatic tertiary
amines such as triethylamine, tributylamine, diisopropylethylamine,
etc.; aliphatic cyclic tertiary amines such as
1,4-diazabicyclo-[2.2.2]octane (DABCO),
1,8-diazabicyclo[5.4.0]undece-7-ene (DBU), etc.; pyridines such as
pyridine, collidine, 4-(N,N-dimethylamino)pyridine, etc.; metal
amides such as lithium amide, sodium amide, etc.; or organometallic
bases such as butyl lithium, s-butyl lithium, lithium
diisopropylamide, sodium bis(trimethylsilyl)amide, lithium
bis(trimethylsilyl)amide, etc.
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, for example, water; alcohols such as
methanol, ethanol, t-butanol, etc.; ketones such as acetone, methyl
isobutyl ketone, etc.; nitriles such as acetonitrile, etc.; esters
such as ethyl acetate, etc.; halogenated hydrocarbons such as
methylene chloride, chloroform, dichloroethane, etc.; ethers such
as diethyl ether, tetrahydrofuran, dioxane, etc.; aromatic
hydrocarbons such as toluene, etc.; amides such as
dimethylformamide, dimethylacetamide, etc.; sulfoxides such as
dimethylsulfoxide, etc.; or a mixed solvent of the above.
When the pyridazine derivative is a base component of a salt, the
salt can be prepared by, for example, mixing the pyridazine
derivative and an acid in the presence or absence of a solvent, and
removing the solvent.
The acid to be used is not specifically limited so long as it is an
acid generally showing a pH of 6 or less, and for example, it may
be inorganic mineral acids such as hydrochloric acid, hydrobromic
acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or organic
acids such as formic acid, acetic acid, toluenesulfonic acid,
oxalic acid, benzoic acid, etc.
The solvent to be used is not specifically limited so long as it
does not inhibit the reaction, and dissolves starting material(s)
with a certain extent, for example, water; alcohols such as
methanol, ethanol, t-butanol, etc.; ketones such as acetone, methyl
isobutyl ketone, etc.; nitriles such as acetonitrile, etc.; esters
such as ethyl acetate, etc.; halogenated hydrocarbons such as
methylene chloride, chloroform, dichloroethane, etc.; ethers such
as diethyl ether, tetrahydrofuran, dioxane, etc.; aromatic
hydrocarbons such as toluene, etc.; amides such as
dimethylformamide, dimethylacetamide, etc.; sulfoxides such as
dimethylsulfoxide, etc.; or a mixed solvent of the above.
The composition of the present invention shows herbicidal activity
against various kinds of weeds which cause problems in a paddy
field, for example, broad-leaved weeds such as Lindernia spp.,
Vandellia angustifolia Benth., Rotala indica, Elatine triandra,
Dopatirum junceum (Roxb.) Hamilt, Ammannia coccinea (Rottb.),
Monochoria vaginaris, etc.; Cyperaceous weeds such as smallflower
umbrella sedge, Scirpus juncoides, needle spikerush, Cyperus
serotinus, Scirpus nipponicus Makino etc.; and Arrowhead plant
weeds such as Sagittaria pygmaea, arrowhead, Alisma canaliculatum,
and shows no crop injury, which causes any problem, to rice.
The composition of the present invention shows herbicidal
activities both by foliar application and soil application against
valious kinds of weeds, which are troublesome in upland fields,
including, for example, broad-leaved weeds such as Common purslane,
Common chickweed, Common lambsquarters, Amaranthus retroflexus L.i,
Sinapis arvensis, shepherdspurse, velvetleaf, Sida spinosa, field
pansy, Cleavers, Lamium purpureum, henbit, Datura stramonium L.,
Solanum nigrum L., Persian speedwell, Matricaria indora, etc.;
Commelinaceae weeds such as asiatic dayflower; and Cyperaceous
weeds such as Cyperus iria, Cyperus rotundus, etc., and shows no
crop injury which causes a problem, against corn, wheat, soybean,
etc.
The composition of the present invention can be used not only in an
upland and a paddy field, but also in an orchard, a mulberry field
and a non-crop land.
Synergistic effects of the present invention can be admitted in a
wide range of a mixing ratio, and when the second herbicidally
active compound is Compound A, B or C, the second herbicidally
active compound is mixed with a ratio of, in general, 0.1 to 50
parts by weight based on 1 part by weight of Compound (I) to
prepare a useful herbicidal composition, and the ratio is
preferably 0.2 to 20 parts by weight, more preferably 0.5 to 10
parts by weight, and when the second herbicidally active compound
is Compound D, E, F or G, the second herbicidally active compound
is mixed with a ratio of, in general, 0.01 to 100 parts by weight
based on 1 part by weight of Compound (I) to prepare a useful
herbicidal composition, and the ratio is preferably 0.02 to 50
parts by weight, more preferably 0.1 to 10 parts by weight. The
thus accomplished herbicidal composition of the present invention
gives high herbicidal effects by applying it before germination of
weeds and subjecting to a soil treatment or a foliar treatment
after germination.
In the present invention, 3-phenoxy-4-pyridazinol derivatives and
the second herbicidally active compound may be mixed and spread as
a preparation, may be spread simultaneously without mixing both
effective ingredients, or may be spread one of these effective
ingredients firstly and then spread the remaining effective
ingredient later. Also, an order of spreading may be optional.
The composition of the present invention may be spread a raw
material itself, or may be used by mixing with a carrier and, if
necessary, with the other auxiliaries, and prepared in a
preparation form which is generally used as a herbicidal
composition, for example, dust powder, coarse dust powder, fine
dust powder, granules, wettable powder, emulsifiable concentrate,
aqueous suspension, water dispersible granules, suspension
concentrate in water or oil, Jumbo (Throw-in Packed) formulation,
etc.
The compound of the present invention is used by mixing with a
carrier and, if necessary, with the other auxiliaries (a
surfactant, etc.), and prepared in a preparation form which is
generally used as a herbicidal composition, for example, dust
powder, coarse dust powder, granules, fine granules, wettable
powder, water-soluble agent, emulsifiable concentrate, liquid
agent, etc. The carrier herein mentioned means a synthetic or
natural inorganic or organic substance which is mixed in the
herbicidal composition to aid reachability of the effective
ingredient compound to plants or to make storage, transportation or
handling of the effective ingredient easy.
A suitable solid carrier may be, for example, clays represented by
kaolinite group, montmorllironite group, attapulgite group, etc.;
inorganic substances such as talc, mica, pyrophyllite, pumice,
vermiculite, gypsum, dolomite, diatomaceous earth, magnesium lime,
phosphorus lime, zeolite, silicic acid anhydride, synthetic calcium
silicate, kaolin, bentonite, calcium carbonate, etc.; vegetable
organic substances such as soybean powder, tobacco powder, walnut
powder, wheat flour, wood powder, starch powder, crystalline
cellulose, etc.; synthetic or natural polymer compounds such as
coumarone resin, petroleum resin, alkyd resin, polyvinyl chloride,
polyalkylene glycol, ketone resin, ester gum, copal gum, dammar
gum, etc.; waxes such as carnauba wax, paraffin wax, bees wax,
etc.; or urea.
Suitable liquid carriers may include, for example, paraffin series
or naphthene series hydrocarbons such as kerosine, mineral oil,
spindle oil, white oil, etc.; aromatic hydrocarbons such as
benzene, toluene, xylene, ethylbenzene, cumene, methylnaphthalene,
etc.; chlorinated hydrocarbons such as carbon tetrachloride,
chloroform, trichloroethylene, monochlorobenzene, chlorotoluene,
etc.; ethers such as dioxane, tetrahydrofuran, etc.; ketones such
as acetone, methylethylketone, diisobutylketone, cyclohexanone,
acetophenone, isophorone, etc.; esters such as ethyl acetate, amyl
acetate, ethylene glycol acetate, diethylene glycol acetate,
dibutyl maleate, diethyl succinate, etc.; alcohols such as
methanol, hexanole, ethylene glycol, diethylene glycol,
cyclohexanol, benzyl alcohol, etc.; ether alcohols such as ethylene
glycol ethyl ether, ethylene glycol phenyl ether, diethylene glycol
ethyl ether, diethylene glycol butyl ether, etc.; polar solvents
such as dimethylformamide, dimethylsulfoxide, etc.; or water.
A surfactant which is used for the purpose of emulsification,
dispersion, wetting, spreading, binding, controlling
disintegration, stabilization of effective ingredient(s),
improvement in fluidity, antirust, promotion of absorption into
plants, etc., may be ionic or nonionic one.
Suitable nonionic surfactants may include, for example, sucrose
ester of aliphatic acid, ethylene oxide polymerized adducts of
higher fatty acids such as lauryl alcohol, stearyl alcohol, oleyl
alcohol, etc., ethylene oxide polymerized adducts of alkylphenols
such as isooctylphenol, nonylphenol, etc., ethylene oxide
polymerized adducts of alkyl naphthol such as butylnaphthol,
octylnaphthol, etc., ethylene oxide polymerized adducts of higher
fatty acids such as palmitic acid, stearic acid, oleic acid, etc.,
ethylene oxide polymerized adducts of mono- or dialkylphosphates
such as stearyl phosphate, dilauryl phosphate, etc., ethylene oxide
polymerized adducts of higher fatty amines such as dodecylamine,
stearic amide, etc., higher fatty acid esters of polyvalent
alcohols such as sorbitan, etc. and their ethylene oxide
polymerized adducts and copolymers of ethylene oxide and propylene
oxide, and the like.
Suitable anionic surfactants may include, for example,
alkylsulfuric acid ester salts such as sodium lauryl sulfate, oleyl
alcohol sulfuric acid ester amine salt, etc., aliphatic acid salts
such as sodium sulfosuccinate dioctyl ester, sodium oleate, sodium
stearate, etc., alkylarylsulfonic acid salts such as sodium
isopropylnaphthalene sulfonate, sodium methylenebisnaphthalene
sulfonate, sodium lignosulfonate, sodium dodecylbenzenesulfonate,
etc.
Suitable cationic surfactants may include, for example, higher
aliphatic amines, quaternary ammonium salts, alkylpyridinium salts,
etc.
Moreover, in the herbicide of the present invention,
A surfactant which is used for the purpose of emulsification,
dispersion, wetting, spreading, binding, controlling
disintegration, stabilization of effective ingredient(s),
improvement in fluidity, antirust, promotion of absorption into
plants, etc., may be ionic or nonionic one.
Suitable nonionic surfactants may include, for example, sucrose
ester of aliphatic acid, ethylene oxide polymerized adducts of
higher fatty acids such as lauryl alcohol, stearyl alcohol, oleyl
alcohol, etc., ethylene oxide polymerized adducts of alkylphenols
such as isooctylphenol, nonylphenol, etc., ethylene oxide
polymerized adducts of alkyl naphthol such as butylnaphthol,
octylnaphthol, etc., ethylene oxide polymerized adducts of higher
fatty acids such as palmitic acid, stearic acid, oleic acid, etc.,
ethylene oxide polymerized adducts of mono- or dialkylphosphates
such as stearyl phosphate, dilauryl phosphate, etc., ethylene oxide
polymerized adducts of higher fatty amines such as dodecylamine,
stearic amide, etc., higher fatty acid esters of polyvalent
alcohols such as sorbitan, etc. and their ethylene oxide
polymerized adducts and copolymers of ethylene oxide and propylene
oxide, and the like.
Suitable anionic surfactants may include, for example,
alkylsulfuric acid ester salts such as sodium lauryl sulfate, oleyl
alcohol sulfuric acid ester amine salt, etc., aliphatic acid salts
such as sodium sulfosuccinate dioctyl ester, sodium oleate, sodium
stearate, etc., alkylarylsulfonic acid salts such as sodium
isopropylnaphthalene sulfonate, sodium methylenebisnaphthalene
sulfonate, sodium lignosulfonate, sodium dodecylbenzenesulfonate,
etc.
Suitable cationic surfactants may include, for example, higher
aliphatic amines, quaternary ammonium salts, alkylpyridinium salts,
etc.
Moreover, in the herbicide of the present invention, for the
purpose of improving characteristics of the preparation and
heightening biological effects, for example, polymer compounds such
as gelatin, Gum Arabic, caseine, albumin, glue, sodium arginate,
polyvinyl alcohol, carboxymethyl cellulose, methyl cellulose,
hydroxymethyl cellulose, etc., thixotropic agents such as sodium
polyphosphate, bentonite, etc. and other auxiliaries may be
contained as other components.
Dust powder or crude dust powder generally contains, for example,
0.1 to 25 parts by weight of an effective ingredient, and the
reminder is a solid carrier.
Wettable powder or granular wettable powder generally contains, for
example, 1 to 90 parts by weight of an effective ingredient, and
the reminder is a solid carrier and a dispersing or wetting agent,
and a protective colloidal agent, thixotropic agent and defoaming
agent are added depending on necessity. These preparations are
suspended and dispersed when they are thrown into water and
stirred.
Granules or fine dust powder generally contain(s), for example, 0.1
to 35 parts by weight of an effective ingredient, and the reminder
is a solid carrier in almost all the part. The effective ingredient
compound is uniformly mixed with a solid carrier, or firmly fixed
or adsorbed on the surface of the solid carrier, and a size of the
grain is generally 0.2 to 1.5 mm.
Emulsifiable concentrate generally contains, for example, 1 to 70
parts by weight of an effective ingredient compound, and further 5
to 20 parts by weight of an emulsifying agent is contained therein,
and the reminder is a liquid carrier, and other auxiliaries such as
a rust proof agent, etc. may be added if necessary.
Aqueous suspension or oil suspension is one in which the effective
ingredient is suspended or emulsified and dispersed in water or an
organic solvent with a high boiling point by using a suitable
surfactant, and stability with a lapse of time is maintained by
adding a thickening agent, etc., if necessary.
The Jumbo (Throw-in Packed) formulation can be prepared by making
an active ingredient suitable preparation forms, for example, dust
powder, granule, tablet, emulsifiable concentrate, clumpy tablet,
etc., and if necessary, they are dividedly packed in a
water-soluble film or a container, and at the time of use, they are
directry thrown into a paddy field with several to several hundred
preparations.
The compound of the present invention thus prepared in various
types of formulations may be applied, for example, at dosage of 1 g
to 1000 g, preferably 10 g to 300 g of an active ingredient per 10
are when it is subjected to soil treatment in a paddy field before
or after germination of weeds, whereby weeds can be effectively
eliminated.
As a method for treating the compound of the present invention, it
can be applied, generally by preparing a formulation, as a soil
treatment, a foliar treatment or a submerged treatment at
pre-emergence or post-emergence within about one month after
germination of weeds. In the soil treatment, there are soil surface
treatment, soil incorporation, etc., in the foliar treatment, in
addition to a treatment from upward of a plant canopy, there is a
directed treatment in which weeds alone are treated so that the
compound is not adhered to crops, etc., and in the submerged
treatment, there are spreading or injection treatment of granules
or flowable agent to water surface, etc.
Into the herbicidal composition of the present invention, other
herbicides may be added to broaden weeding spectrum.
The herbicidal composition of the present invention can be used by
mixing with, for example, a plant growth regulator, fungicide,
insecticide, acaricide, nematocide or fertilizer, etc.
BEST MODE FOR CARRYING OUT THE INVENTION
In the following, Examples, Preparation examples and Test examples
of the present invention are shown to explain the invention more
specifically, but the present invention is not limited by these.
Incidentally, in the following Preparation examples, "%" means % by
weight.
EXAMPLE 1
6-Chloro-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 128)
(1) 3-Chloro-6-(2-methylphenoxy)pyridazine (Step A-1)
A mixture of 278.7 g (1.87 mol) of 3,6-dichloropyridazine, 202.3 g
(1.87 mol) of 2-methylphenol and 259 g (1.87 mol) of potassium
carbonate was stirred at 160.degree. C. for 6 hours. The reaction
mixture was cooled to 70.degree. C. and 2 L of ethyl acetate was
added. This mixture was washed successively with 1 mol/L sodium
hydroxide aqueous solution (4.times.500 mL), water (4.times.500 mL)
and brine (50 mL), and dried over anhydrous magnesium sulfate. The
solvent was removed, and isopropyl ether was added to the residue
to form crystal. The crystal was collected by filtration to obtain
234.2 g (1.06 mol, Yield: 56.7%) of
3-chloro-6-(2-methylphenoxy)pyridazine.
(2) 4,6-Dichloro-3-(2-methylphenoxy)pyridazine (Step A-2)
In phosphorus oxychloride (1.85 L) was dissolved
6-chloro-3-(2-methylphenoxy)pyridazine (234.2 g, 1.06 mol) obtained
in (1), and 76.7 g (1.08 mol) of a chlorine gas was passed into the
solution over 4 hours. A nitrogen gas was passed into the reaction
mixture to remove excess chlorine gas, and then phosphorus
oxychloride was removed. The residue was dissolved in ethyl acetate
(1.5 L), washed successively with water (4.times.500 mL) and
brine(200 mL), and dried over anhydrous magnesium sulfate. The
solvent was removed, and the resulting residue was washed with 500
mL of hexane to obtain 193.1 g of a crude product. This crude
product was recrystallized form a mixed solvent of hexaneethyl
acetate (400 mL-240 mL) to obtain 114.4 g (0.448 mol, Yield: 42.3%)
of 4,6-dichloro-3-(2-methylphenoxy)pyridazine.
(3) 6-Chloro-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 128,
Step A-3)
In 1,4-dioxane (1 L) was dissolved 100.0 g (0.392 mol) of
4,6-dichloro-3-(2-methylphenoxy)pyridazine obtained in (2), and to
the solution were added an aqueous solution (400 mL of water)
containing sodium hydroxide (purity 96%, 19.6 g, 0.470 mol) and
1.09 g (4.78 mmol) of tetrabutylammonium chloride, and the
resulting mixture was stirred for 4 hours under reflux. The
reaction mixture was concentrated under reduced pressure, and the
total amount was made about 100 mL. To the residue were added an
aqueous sodium hydroxide solution (13.1 g of sodium hydroxide was
dissolved in 1.4 L of water) and 500 mL of ethyl acetate. The
aqueous layer was washed with ethyl acetate (3.times.200 mL),
cooled in an ice-bath, and then conc. hydrochloric acid was added
to adjust the pH thereof to 5. Precipitated solid was collected by
suction filtration, washed with 1 L of water and air dried. The
resulting solid was recrystallized from acetonitrile to obtain 34.4
g (0.145 mol, Yield: 37.0%) of
6-chloro-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 128).
Also, the organic layer was dried over magnesium sulfate, and the
solvent was removed. The obtained residue was purified by silica
gel column chromatography (YMC GEL, SIL60, 350/250 mesh,
hexane-ethyl acetate, gradient) to obtain 13.5 g (0.0414 mol,
Yield: 10.5%) of 6-chloro-3,4-bis(2-methylphenoxy)pyridazine.
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.35-7.08 (4H, m),
6.84 (1H, brs), 2.11 (3H, s). Melting point (.degree. C.):
211-213.
EXAMPLE 2
3-(2-Methylphenoxy)-4-pyridazinol (Compound No. 5)
(1) 6-Chloro-4-methoxy-3-(2-methylphenoxy)pyridazine (Step A-3)
In methanol (60 mL) was dissolved 3.00 g (11.8 mmol) of
4,6-dichloro-3-(2-methylphenoxy)pyridazine obtained in Example 1
(2), 1.00 g (17.6 mmol) of 95% sodium methoxide was added to the
solution at room temperature and the mixture was stirred at
60.degree. C. for 4 hours. Moreover, 1.00 g (17.6 mmol) of 95%
sodium methoxide was further added and after stirring the mixture
at 60.degree. C. for 1 hour, it was allowed to stand at room
temperature overnight. The reaction mixture was concentrated, ethyl
acetate was added to the residue, and the mixture was successively
washed with water and brine. After drying over anhydrous sodium
sulfate, the solvent was removed, and the obtained residue was
purified by silica gel column chromatography (eluted with
hexane:ethyl acetate=4:1) to obtain 2.75 g (11.0 mmol, Yield:
93.2%) of 6-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine.
(2) 4-Methoxy-3-(2-methylphenoxy)pyridazine (Step N-1)
In methanol (40 mL) was dissolved 2.00 g (7.98 mmol) of
6-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in (1),
0.20 g of 5% palladium-carbon was added to the solution and the
mixture was stirred under hydrogen atmosphere (1 atm) for 4 hours.
The reaction mixture was filtered through Celite, and the filtrate
was concentrated. The residue was purified by silica gel column
chromatography (eluted with ethyl acetate and then dichloromethane:
methanol=5:1) to obtain 1.59 g (7.36 mmol, Yield: 92.2%) of
4-methoxy-3-(2-methylphenoxy)pyridazine.
(3) 3-(2-Methylphenoxy)-4-pyridazinol (Compound No. 5, Step
N-2)
A mixture comprising 1.08 g (5.00 mmol) of
4-methoxy-3-(2-methylphenoxy)pyridazine obtained in (2), 0.24 g
(6.0 mmol) of sodium hydroxide, water (5 mL) and 1,4-dioxane (5 mL)
was stirred overnight. The reaction mixture was washed with ethyl
acetate, the aqueous layer was made acidic with hydrochloric acid,
and extracted with ethyl acetate. The solvent was removed to obtain
0.21 g (10 mmol, Yield: 20%) of 3-(2-methylphenoxy)-4-pyridazinol
(Compound No. 5).
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 8.30 (1H, d, J=7.2
Hz), 7.43-7.00 (5H, m), 6.43 (1H, d, J=7.2 Hz), 2.18 (3H, s).
Melting point (.degree. C.): 169-171.
EXAMPLE 3
5-Chloro-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 45)
(1) 4,5-Dichloro-3-(2-methylphenoxy)pyridazine
16.4 g (88.2 mmol) of 3-(2-methylphenoxy)pyridazine {which can be
produced by the method described in Agricultural and Biological
Chemistry, 1968, vol. 32, p. 1376 and Agricultural and Biological
Chemistry, 1969, vol. 33, p. 96.} and phosphorus oxychloride (200
mL) were mixed, the mixture was heated to 80.degree. C., and 8.5 g
(120 mmol) of a chlorine gas was introduced therein. Phosphorus
oxychloride was removed from the reaction mixture by distillation,
the residue was poured into ice-cold water, and extracted with
ethyl acetate. The organic layers were combined, washed with water,
and dried over anhydrous sodium sulfate. The solvent was removed,
and the residue was purified by silica gel column chromatography
(available from Merck Co., 9385, hexane:ethyl acetate gradient) to
obtain 6.61 g (25.9 mmol, Yield: 29.4%) of
4,5-dichloro-3-(2-methylphenoxy)pyridazine, 8.14 g (36.9 mmol,
Yield: 41.8%) of 5-chloro-3-(2-methylphenoxy)pyridazine and 1.20 g
(5.44 mmol, Yield: 6.17%) of
4-chloro-3-(2-methylphenoxy)pyridazine.
(2) 5-Chloro-4-methoxy-3-(2-methylphenoxy)pyridazine (Step A-3)
5.10 g (20.0 mmol) of 4,5-dichloro-3-(2-methylphenoxy)pyridazine
obtained in (1) and methanol (70 mL) were mixed, and 0.46 g (20
mmol) of sodium was added to the mixture at -8.degree. C., and the
resulting mixture was stirred at -8.degree. C. for 30 minutes, and
in an ice bath for 8 hours and 30 minutes. Ice-cold water was added
to the reaction mixture, pH was made 3 with hydrochloric acid, and
then the mixture was extracted with ethyl acetate. The organic
layers were combined, washed with water, and dried over anhydrous
sodium sulfate. The solvent was removed, and the residue was
purified by silica gel column chromatography (available from Merck
Co., 9385, hexane:ethyl acetate, gradient) to obtain 1.15 g (4.58
mmol, Yield: 22.9%) of
5-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine and 3.27 g (13.0
mmol, Yield: 65%) of
4-chloro-5-methoxy-3-(2-methylphenoxy)pyridazine.
(3) 5-Chloro-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 45,
Step A-4, etc.)
750 mg (2.99 mmol) of
5-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in (2),
156 mg (3.9 mmol) of sodium hydroxide, 1,4-dioxane (5 mL) and water
(10 mL) were mixed, and the mixture was refluxed with stirring for
2 hours and 30 minutes. The reaction mixture was poured into
ice-cold water, and made acidic with hydrochloric acid. The
precipitated solid was collected by filtration, and washed with
water and then with hexane. 525 mg (2.22 mmol, Yield: 74.2%) of
5-chloro-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 45) was
obtained.
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 8.68 (1H, s),
7.38-6.80 (4H, m), 5.32 (1H, brs), 2.13 (3H, s). Melting point
(.degree. C.): 238-243.
EXAMPLE 4
5-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 4-methylbenzene
sulfonate (Compound No. 66, Step I-1)
237 mg (1.00 mmol) of 5-chloro-3-(2-methylphenoxy)-4-pyridazinol
(Compound No. 45) obtained in Example 3 and acetonitrile (8 mL)
were mixed, and 112 mg (1.00 mmol) of 1,4-diazabicyclo[2,2,2]octane
was added to the mixture with stirring, and then, 191 mg (1.00
mmol) of 4-methylbenzene sulfonyl chloride was added thereto, and
the resulting mixture was stirred at room temperature for 1 hour
and 30 minutes. Water was added to the reaction mixture, the
mixture was made acidic with hydrochloric acid, and extracted with
ethyl acetate. The organic layers were combined, washed with water,
and dried over anhydrous sodium sulfate. The solvent was removed,
and the residue was purified by silica gel column chromatography
(Wako gel C-100, hexane:ethyl acetate=3:1) to obtain 379 mg (0.969
mmol, Yield: 96.9%) of 5-chloro-3-(2-methylphenoxy)-4-pyridazinyl
4-methylbenzene sulfonate (Compound No. 66).
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.80 (1H, s),
7.77-6.75 (8H, m), 2.47 (3H, s), 1.98 (3H, s). Melting point
(.degree. C.): 140-143.
EXAMPLE 5
6-Chloro-3-(2-methylphenoxy)-4-pyridazinol 1-oxide (Compound No.
129, Step F-1)
135 mg (0.572 mmol) of 6-chloro-3-(2-methylphenoxy)-4-pyridazinol
(Compound No. 128) obtained in Example 1 and methylene chloride (6
mL) were mixed, 247 mg (purity 80%, 1.14 mmol) of
m-chloroperbenzoic acid was added to the mixture and the resulting
mixture was refluxed for 16 hours with stirring. The mixture was
allowed to stand at room temperature for 2 days, the reaction
mixture was poured in a saturated aqueous sodium sulfite solution,
and washed with methylene chloride. The aqueous layer was made
acidic with hydrochloric acid, extracted with methylene chloride,
then washed with brine, and dried over anhydrous sodium sulfate.
The solvent was removed, and the obtained residue was purified by
silica gel column chromatography (YMC GEL, SIL60, 350/250 mesh,
eluted with ethyl acetate) to obtain 32.6 mg (0.129 mmol, Yield:
22.6%) of 6-chloro-3-(2-methylphenoxy)-4-pyridazinol 1-oxide
(Compound No. 129).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.34 (1H, s),
7.34-7.10 (4H, m), 2.20 (3H, s). Melting point (.degree. C.):
194-196.
EXAMPLE 6
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinol (Compound No.
139)
(1) Mixture of 6-chloro-3-(2-cyclopropylphenoxy)pyridazine 1-oxide
and 3-chloro-6-(2-cyclopropylphenoxy)pyridazine 1-oxide (Step
B-2)
25.3 g (189 mmol) of 2-cyclopropylphenol, 1,4-dioxane (120 mL) and
dimethylsulfoxide (120 mL) were mixed, 23.2 g (207 mmol) of
potassium tert-butoxide was added to the mixture in an ice bath and
the resulting mixture was stirred for 10 minutes. To the mixture
was added 32.0 g (194 mmol) of 3,6-dichloropyridazine 1-oxide which
is a known compound, and the mixture was allowed to stand at room
temperature for 5 days. The reaction mixture was poured into
ice-cold water, and extracted with ethyl acetate. The organic
layers were combined, washed successsively with water and brine,
and dried over anhydrous sodium sulfate. The solvent was removed,
and the residue was purified by silica gel column chromatography
(hexane:ethyl acetate, gradient) to obtain 43.3 g (165 mmol, Yield:
87.3%) of a mixture of 6-chloro-3-(2-cyclopropylphenoxy)pyridazine
1-oxide and 3-chloro-6-(2-cyclopropylphenoxy)pyridazine
1-oxide.
(2) 4,6-Dichloro-3-(2-cyclopropylphenoxy)pyridazine (Step B-3)
43.3 g (165 mmol) of a mixture of
6-chloro-3-(2-cyclopropylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-cyclopropylphenoxy)pyridazine 1-oxide obtained in
(1), chloroform (30 mL) and 18.0 mL (194 mmol) of phosphorus
oxychloride were mixed, and the mixture was heated to 60.degree. C.
and dissolved. The solution was stirred at room temperature
overnight, and concentrated. The residue was purified by silica gel
column chromatography (hexane:ethyl acetate, gradient) to obtain
32.5 g (116 mmol, Yield: 70.3%) of
4,6-dichloro-3-(2-cyclopropylphenoxy)pyridazine.
(3) 6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinol (Compound No.
139, Step B-4)
In dimethylsulfoxide (500 mL) was dissolved 32.5 g (116 mmol) of
4,6-dichloro-3-(2-cyclopropylphenoxy)pyridazine obtained in (2), 84
mL (210 mmol) of 10% (w/v) aqueous sodium hydroxide solution was
added to the solution, and the mixture was stirred at room
temperature overnight. The reaction mixture was poured into
ice-cold 1 mol/L aqueous sodium hydroxide solution, and washed with
ether. The aqueous layer was made acidic with hydrochloric acid,
the precipitated solid was collected by filtration, and washed with
water. To the resulting solid was added acetonitrile and the
mixture was heated. The mixture was cooled overnight by allowing to
stand, and crystals (14.04 g) were collected by filtration. The
filtrate was concentrated, the residue was recrystallized from
ethanol to obtain 2.64 g of crystals. These crystals were combined
to obtain 16.7 g (63.5 mmol, Yield: 54.7%) of
6-chloro-3-(2-cyclopropylphenoxy)-4-pyridazinol (Compound No.
139).
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.28-6.97 (4H, m),
6.82 (1H, s), 1.89-1.77 (1H, m), 0.87-0.73 (2H, m), 0.73-0.58 (2H,
m). Melting point (.degree. C.): 229-231.
EXAMPLE 7
6-Chloro-3-[2-(1-fluorocyclopropyl)phenoxy]-4-pyridazinol (Compound
No. 140)
(1) 2-(Methoxymethoxy)benzaldehyde
In N,N-dimethylformamide (20 mL) was dissolved 5.01 g (41.1 mmol)
of commercially available salicylaldehyde, 1.80 g (45.0 mmol) of
60% sodium hydride was added to the solution in an ice bath, and
after stirring the mixture in an ice bath for 10 minutes, 3.43 mL
(45.2 mmol) of chloro(methoxy)methane was gradually added dropwise
to the mixture and the resulting mixture was stirred in an ice bath
for 1 hour. The reaction mixture was poured into water, and
extracted with ethyl acetate. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was removed, and the obtained residue was
purified by silica gel column chromatography (Wako gel C-100,
hexane-ethyl acetate, gradient) to obtain 6.54 g (39.4 mmol, Yield:
95.9%) of 2-(methoxymethoxy)benzaldehyde.
(2) 1-(Methoxymethoxy)-2-vinylbenzene
Under nitrogen atmosphere, 877 mg (21.9 mmol) of 60% sodium hydride
washed with hexane was suspended in dry dimethylsulfoxide (10 mL),
the suspension was heated at 85.degree. C. for 30 minutes with
stirring, cooled to room temperature, and then, in an ice bath, a
dry dimethylsulfoxide (20 mL) solution containing 7.83 g (21.9
mmol) of methyl(triphenyl)phosphonium bromide was gradually added
dropwise thereto. After stirring at room temperature for 15
minutes, a dry dimethylsulfoxide (9 mL) solution containing 3.02 g
(18.2 mmol) of 2-(methoxymethoxy)benzaldehyde obtained in (1) was
added dropwise thereto, and the mixture was stirred at room
temperature for 15 minutes. The reaction mixture was poured into
water, and extracted with diethyl ether. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane-ethyl acetate, gradient) to obtain 2.54 g (15.5 mmol,
Yield: 85.2%) of 1-(methoxymethoxy)-2-vinylbenzene.
(3) 1-(2-Bromo-1-fluoroethyl)-2-(methoxymethoxy)benzene
To a methylene chloride (10 mL) solution containing 1.47 g (9.13
mmol) of N,N,N-triethylamine hydrotrifluoric acid (MEC-82) was
added dropwise a methylene chloride (5 mL) solution containing 1.00
g (6.09 mmol) of 1-(methoxymethoxy)-2-vinylbenzene obtained in (2),
and 1.19 g (6.70 mmol) of N-bromosuccinimide was added thereto in
an ice bath. The mixture was stirred in an ice bath as such for 2
hours, it was warmed to room temperature and stirred for further 30
minutes. The reaction mixture was poured into a saturated aqueous
sodium hydrogen carbonate solution and extracted with methylene
chloride. The organic layer was successively washed with diluted
hydrochloric acid, water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05717, 4 plates were used, developed
by ethyl acetate:hexane=4:1), and then, purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 4
plates were used, developed by ethyl acetate:hexane=10:1) to obtain
1.24 g of a crude product of
1-(2-bromo-1-fluoroethyl)-2-(methoxymethoxy)benzene.
(4) 1-(1-Fluorovinyl)-2-(methoxymethoxy)benzene
In dry dimethylsulfoxide (10 mL) was added 736.2 mg (11.15 mmol) of
85% potassium hydroxide, the mixture was stirred at room
temperature for 1 hour and 30 minutes, a dry dimethylsulfoxide (6
mL) solution containing 978.2 mg of a crude purified product of
1-(2-bromo-1-fluoroethyl)-2-(methoxymethoxy)benzene obtained in (3)
was added dropwise to the mixture, and the resulting mixture was
stirred for 2 hours and then stirred at 60.degree. C. for 2 hours.
The reaction mixture was poured into water and extracted with
hexane. The organic layer was successively washed with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
removed to obtain 632.7 mg of a crude product of
1-(1-fluorovinyl)-2-(methoxymethoxy)benzene.
(5) 1-(1-Fluorocyclopropyl)-2-(methoxymethoxy)benzene
Under nitrogen atmosphere, dry diethyl ether (5 mL) was charged in
a dry flask, 1.97 mL (1.97 mmol) of diethylzinc (1M hexane
solution) was added dropwise thereto, and then, a dry diethyl ether
(3 mL) solution containing 143.6 mg of a crude product of
1-(1-fluorovinyl)-2-(methoxymethoxy)benzene obtained in (4) was
added dropwise thereto. After stirring at room temperature for 10
minutes, 0.19 mL (2.3 mmol) of diiodomethane was added dropwise to
the mixture and the resulting mixture was refluxed for 4 hours and
30 minutes. The reaction mixture was poured into a saturated
aqueous ammonium chloride solution, then, a saturated aqueous
sodium hydrogen carbonate solution was added and the mixture was
stirred for a while, and extracted with diethyl ether. The organic
layer was successively washed with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was distilled off and the
obtained residue was purified by preparative thin-layer
chromatography (available from MERCK CO., 1.05744, 3 plates were
used, developed by ethyl acetate:hexane=4:1) to obtain 80.5 mg of a
crude product of
1-(1-fluorocyclopropyl)-2-(methoxymethoxy)benzene.
(6) 2-(1-Fluorocyclopropyl)phenol
Conc. hydrochloric acid (0.3 mL) was added dropwise to a methanol
(6 mL) solution containing 43.8 mg of a crude product of
1-(1-fluorocyclopropyl)-2-(methoxymethoxy)benzene obtained in (5),
and the mixture was stirred at 60.degree. C. for 3 hours. The
reaction mixture was poured into water, and extracted with ethyl
acetate. The organic layer was successively washed with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
removed to obtain 42.8 mg of a crude product of
2-(1-fluorocyclopropyl)phenol.
(7) 6-Chloro-3-[2-(1-fluorocyclopropyl)phenoxy]pyridazine 1-oxide
(Step B-2)
In a mixed solvent of 1,4-dioxane(3 mL) and dimethylsulfoxide (3
mL) was dissolved 42.8 mg of a crude product of
2-(1-fluorocyclopropyl)phenol obtained in (6), 34.7 mg (0.310 mmol)
of potassium tert-butoxide was added to the solution, and then,
46.4 mg.(0.281 mmol) of 3,6-dichloropyridazine 1-oxide was added to
the mixture and the resulting mixture was stirred at room
temperature overnight. The reaction mixture was poured into water,
and extracted with ethyl acetate. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 2 plates were used, developed
by ethyl acetate:hexane=2:1) to obtain 28.0 mg (0.0996 mmol) of
6-chloro-3-[2-(1-fluorocyclopropyl)phenoxy]pyridazine 1-oxide.
(8) 4,6-Dichloro-3-[2-(1-fluorocyclopropyl)phenoxy]-pyridazine
(Step B-3)
In phosphorus oxychloride (1 mL) was dissolved 28.0 mg (0.0996
mmol) of 6-chloro-3-[2-(1-fluorocyclopropyl)phenoxy]pyridazine
1-oxide obtained in (7), and the solution was stirred at room
temperature overnight. To the mixture were added water and
methylene chloride, and after stirring for 30 minutes, the mixture
was extracted with methylene chloride. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 2 plates were used, developed
by ethyl acetate:hexane=2:1) to obtain 5.1 mg (0.017 mmol, Yield:
17%) of
4,6-dichloro-3-[2-(1-fluorocyclopropyl)phenoxy]pyridazine.
(9) 6-Chloro-3-[2-(1-fluorocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 140, Step B-4)
In a mixed solvent of 1,4-dioxane (2 mL) and dimethylsulfoxide (2
mL) was dissolved 5.1 mg (0.017 mmol) of
4,6-dichloro-3-[2-(1-fluorocyclopropyl)phenoxy]pyridazine obtained
in (8), and to the solution was added 0.1 mL of 2 mol/L of aqueous
sodium hydroxide solution, and the resulting mixture was stirred at
room temperature overnight. The reaction mixture was poured into
water, diluted hydrochloric acid was added to the mixture to adjust
pH 2, and extracted with ethyl acetate. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 1 plate was used, developed by
ethyl acetate) to obtain 4.0 mg (0.014 mmol, Yield: 82%) of
6-chloro-3-[2-(1-fluorocyclopropyl)phenoxy]-4-pyridazinol (Compound
No. 140).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.57-7.52 (1H, m),
7.39-7.31 (1H, m), 7.22-7.13 (1H, m), 7.00 (1H, d, J=8.1 Hz), 6.48
(1H, s), 1.32-1.22 (2H, m), 1.16-1.08 (2H, m). Melting point
(.degree. C.): 152-157.
EXAMPLE 8
6-Chloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]phenoxy}-4-pyridazinol
(Compound No. 207)
(1) 1-Methoxy-2-vinylbenzene
Under nitrogen atmosphere, in dry dimethylsulfoxide (15 mL) was
suspended 1.92 g (48.0 mmol) of 60% sodium hydride washed with
hexane, after stirring the suspension at 85.degree. C. for 30
minutes, it was cooled to room temperature and then, in an ice
bath, a dry dimethylsulfoxide (35 mL) solution containing 17.2 g
(48.2 mmol) of methyl(triphenyl)phosphonium bromide was gradually
added dropwise thereto. After stirring at room temperature for 20
minutes, 4.83 mL (40.1 mmol) of commercially available
2-methoxybenzaldehyde was added dropwise thereto, and the resulting
mixture was stirred at room temperature for 1 hour and then at
65.degree. C. for 3 hours. The reaction mixture was poured into ice
water, and extracted with ethyl acetate. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane-ethyl acetate, gradient) to obtain 3.29 g (24.5 mmol,
Yield: 61.1%) of 1-methoxy-2-vinylbenzene.
(2) 1-(2-Bromo-1-fluoroethyl)-2-methoxybenzene
To a methylene chloride (20 mL) solution containing 3.60 g (22.4
mmol) of N,N,N-triethylamine hydrotrifluoric acid (MEC-82) was
added dropwise a methylene chloride (6 mL) solution containing 2.01
g (15.0 mmol) of 1-methoxy-2-vinylbenzene obtained in (1), and 2.92
g (16.4 mmol) of N-bromosuccinimide was added in an ice bath.
Stirring was continued in an ice bath for 25 minutes, and the
mixture was warmed to room temperature and further stirred for 1
hour and 30 minutes. The reaction mixture was poured into a
saturated aqueous sodium hydrogen carbonate solution and extracted
with methylene chloride. The organic layer was successively washed
with diluted hydrochloric acid, water and brine, and dried over
anhydrous magnesium sulfate. The solvent was removed, and the
obtained residue was purified by silica gel column chromatography
(Wako gel C-100, hexane-ethyl acetate, gradient) to obtain 1.39 g
of a crude product of
1-(2-bromo-1-fluoroethyl)-2-methoxybenzene.
(3) 1-(1-Fluorovinyl)-2-methoxybenzene
To dry dimethylsulfoxide (10 mL) was added 1.28 g (19.4 mmol) of
85% potassium hydroxide, the mixture was stirred at room
temperature for 30 minutes, and then, a dry dimethylsulfoxide (10
mL) solution containing 1.50 g of a crude product of
1-(2-bromo-1-fluoroethyl)-2-methoxybenzene obtained in (2) was
added dropwise thereto, and the mixture was stirred overnight. The
reaction mixture was poured into water and extracted with hexane.
The organic layer was successively washed with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was removed,
and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate, gradient) to
obtain 1.21 g of a crude product of
1-(1-fluorovinyl)-2-methoxybenzene.
(4) 1-(1-Fluorocyclopropyl)-2-methoxybenzene
Under nitrogen atmosphere, dry diethyl ether (8 mL) was charged in
a dry flask, 19.88 mL (19.88 mmol) of diethylzinc (1 mol/L hexane
solution) was added dropwise thereto, and a dry diethyl ether (8
mL) solution containing 1.21 g of a crude product of
1-(1-fluorovinyl)-2-methoxybenzene obtained in (3) was added
dropwise thereto. After stirring at room temperature for 10
minutes, 1.92 mL (23.86 mmol) of diiodomethane was added dropwise
thereto, and the mixture was refluxed for 6 hours. After allowing
to stand at room temperature overnight, the reaction mixture was
poured into a saturated aqueous ammonium chloride solution, and
then, a saturated aqueous sodium hydrogen carbonate solution was
added thereto and the mixture was stirred for a while, and
extracted with diethyl ether. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was removed, and the obtained residue was
purified by silica gel column chromatography (Wako gel C-100,
hexane-ethyl acetate, gradient) to obtain 1.06 g of a crude product
of 1-(1-fluorocyclopropyl)-2-methoxybenzene.
(5) 2-[1-(ethylsulfanyl)cyclopropyl]phenol
Under nitrogen atmosphere, in dry N,N-dimethylformamide (8 mL) was
suspended 765.3 mg (19.1 mmol) of 60% sodium hydride, and to the
suspension was gradually added dropwise 1.46 mL (19.8 mmol) of
ethanethiol and after stirring for 15 minutes, a dry
N,N-dimethylformamide (5 mL) solution containing 1.06 g of a crude
product of 1-(1-fluorocyclopropyl)-2-methoxybenzene obtained in (4)
was added dropwise thereto and the resulting mixture was stirred at
160.degree. C. for 5 hours. After cooling by allowing to stand, 1
mol/L of aqueous potassium hydroxide solution and diethyl ether
were added to the reaction mixture. The aqueous layer was
separated, and washed with diethyl ether. To the mixture was added
diluted hydrochloric acid to adjust pH to 2, and extracted with
diethyl ether. The organic layer was successively washed with water
and brine, and dried over anhydrous magnesium sulfate. The solvent
was removed, and the obtained residue was purified by silica gel
column chromatography (Wako gel C-100, hexaneethyl acetate,
gradient) to obtain 0.26 g of a crude product of
2-[1-(ethylsulfanyl)cyclopropyl]phenol.
(6) 6-Chloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]phenoxy}-pyridazine
1-oxide (Step B-2)
In a mixed solvent of 1,4-dioxane (3 mL) and dimethylsulfoxide (3
mL) was dissolved 0.26 g of a crude product of
2-[1-(ethylsulfanyl)cyclopropyl]phenol obtained in (5), 265.5 mg
(2.37 mmol) of potassium tert-butoxide was added to the solution,
and then, 390.3 mg (2.37 mmol) of 3,6-dichloropyridazine 1-oxide
was added to the same, and the resulting mixture was stirred at
room temperature overnight. The reaction mixture was poured into
water, and extracted with ethyl acetate. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 3 plates were used, developed
by ethyl acetate:hexane=2:1) to obtain 138.4 mg (0.428 mmol) of
6-chloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]phenoxy}pyridazine
1-oxide.
(7)
4,6-Dichloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]-phenoxy}pyridazine
(Step B-3)
In phosphorus oxychloride (1 mL) was dissolved 138.4 mg (0.428
mmol) of
6-chloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]phenoxy}pyridazine
1-oxide obtained in (6), and the solution was stirred at room
temperature overnight. To the reaction mixture were added water and
methylene chloride, and the mixture was stirred for 30 minutes and
extracted with methylene chloride. The organic layer was
successsively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 2 plates were used, developed
by ethyl acetate:hexane=4:1) to obtain 94.4 mg (0.277 mmol, Yield:
64.7%) of
4,6-dichloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]phenoxy}pyridazine.
(8)
6-Chloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]phenoxy}-4-pyridazinol
(Compound No. 207, Step B-4)
In a mixed solvent of 1,4-dioxane (1 mL) and dimethylsulfoxide (1
mL) was dissolved 94.4 mg (0.277 mmol) of
4,6-dichloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]phenoxy}pyridazine
obtained in (7), 0.69 mL (1.38 mmol) of 2 mol/L aqueous sodium
hydroxide solution was added to the solution, and the mixture was
stirred at room temperature overnight. To the reaction mixture were
added water and ethyl acetate, the aqueous layer was separated and
washed with ethyl acetate. Diluted hydrochloric acid was added
thereto to adjust pH to 2, and the mixture was extracted with ethyl
acetate. The organic layer was successively washed with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 2
plates were used, developed by ethyl acetate) to obtain 47.5 mg
(0.147 mmol, Yield: 53.1%) of
6-chloro-3-{2-[1-(ethylsulfanyl)cyclopropyl]phenoxy}-4-pyridazinol
(Compound No. 207).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.45-7.07 (4H, m),
6.69 (1H, s), 2.46 (2H, q, J=7.3 Hz), 1.28-1.02 (9H, m). Melting
point (.degree. C.): 88.
EXAMPLE 9
6-Chloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 265)
(1) 1-(2,2-dichlorocyclopropyl)-2-(methoxymethoxy)benzene
In chloroform (12 mL) was dissolved 305 mg (1.86 mmol) of
1-(methoxymethoxy)-2-vinylbenzene obtained in Example 7(2), 5 mL
(63 mmol) of 50% aqueous sodium hydroxide solution was added
dropwise to the solution, and then, 54.1 mg (0.237 mmol) of
benzyl(triethyl)ammonium chloride was added to the same and the
resulting mixture was stirred at room temperature overnight. The
reaction mixture was poured into water, and extracted with
chloroform. The organic layer was successively washed with water
and brine, and dried over anhydrous magnesium sulfate. The solvent
was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 3 plates were used, developed by ethyl acetate:hexane=1:2)
to obtain 387 mg (1.57 mmol, Yield: 84.4%) of
1-(2,2-dichlorocyclopropyl)-2-(methoxymethoxy)benzene.
(2) 2-(2,2-Dichlorocyclopropyl)phenol
In methanol (5 mL) was dissolved 203 mg (0.822 mmol) of
1-(2,2-dichlorocyclopropyl)-2-(methoxymethoxy)benzene obtained in
(1), 0.1 mL of conc. hydrochloric acid was added to the solution,
and the resulting mixture was stirred at 60.degree. C. for 2 hours.
After confirming disappearance of the starting materials by thin
layer chromatography, the reaction mixture was poured into water,
and extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed to obtain 194 mg of a
crude product of 2-(2,2-dichlorocyclopropyl)phenol.
(3) 6-Chloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]-pyridazine
1-oxide (Step B-2)
In a mixed solvent of 1,4-dioxane (3 mL) and dimethylsulfoxide (3
mL) was mixed 194 mg of a crude product of
2-(2,2-dichlorocyclopropyl)phenol obtained in (2), 118 mg (1.05
mmol) of potassium tert-butoxide was added to the mixture in an ice
bath, and the resulting mixture was stirred for 10 minutes. To the
mixture was added 157 mg (0.952 mmol) of 3,6-dichloropyridazine
1-oxide, and the mixture was stirred at room temperature overnight.
The reaction mixture was poured into ice-cold water, and extracted
with ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the residue
was purified by preparative thin-layer chromatography (available
from MERCK CO., 1.05744, 3 plates were used, developed by ethyl
acetate:hexane=1:2) to obtain 268 mg of a crude product of
6-chloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]pyridazine
1-oxide.
(4) 4,6-Dichloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]-pyridazine
(Step B-3)
268 mg of a crude product of
6-chloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]pyridazine 1-oxide
obtained in (3) and 3 mL of phosphorus oxychloride were mixed, and
the mixture was stirred at room temperature overnight. To the
reaction mixture were added water and dichloromethane, and the
resulting mixture was stirred for 30 minutes. The mixture was
separated, and the organic layer was successively washed with water
and brine, and dried over anhydrous magnesium sulfate. The solvent
was distilled off and the residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 3
plates were used, developed by ethyl acetate:hexane=1:2) to obtain
162 mg (0.463 mmol, Yield with 3 steps from
1-(2,2-dichlorocyclopropyl)-2-(methoxymethoxy)benzene: 56.3%) of
4,6-dichloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]pyridazine.
(5) 6-Chloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 265, Step B-4)
162 mg (0.463 mmol) of
4,6-dichloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]pyridazine
obtained in (4), 1,4-dioxane (3 mL) and dimethylsulfoxide (3 mL)
were mixed, to the mixture was added 1.15 mL (2.30 mmol) of 2 mol/L
aqueous sodium hydroxide solution, and the mixture was stirred at
room temperature overnight. The reaction mixture was poured into
water, and made acidic with diluted hydrochloric acid. The mixture
was extracted with dichloromethane. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was distilled off and the
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 3 plates were used, developed
by ethyl acetate) to obtain 50.0 mg (0.151 mmol, Yield: 32.6%) of
6-chloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 265).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.55-7.15 (4H, m),
6.69 (1H, s), 2.90 (1H, dd, J=10.6, 8.8 Hz), 2.07-1.89 (2H, m).
Melting point (.degree. C.): 158-163.
EXAMPLE 10
6-Chloro-3-(2-hydroxyphenoxy)-4-pyridazinol (Compound No. 384)
(1) 3-Chloro[1,4]benzodioxino[2,3-c]pyridazine(Step O-1)
In 1,4-dioxane (30 mL) was suspended 3.49 g (80.0 mmol) of 55%
sodium hydride, and to the suspension were added a 1,4-dioxane (30
mL) solution containing 4.40 g (40 mmol) of pyrocatechol, then a
1,4-dioxane (30 mL) solution containing 7.30 g (39.9 mmol) of
3,4,6-trichloropyridazine {described in The Journal of Organic
Chemistry, 1963, vol. 28, pp. 218 to 221}, and the mixture was
refluxed for 2 hours. The reaction mixture was poured into ice-cold
water, and extracted with ethyl acetate. The organic layers were
combined, washed successively with 1 mol/L sodium hydroxide and
water, and dried over anhydrous magnesium sulfate. The solvent was
removed, and the residue was recrystallized from methyl isobutyl
ketone to obtain 6.15 g (27.8 mmol, Yield: 69.7%) of
3-chloro[1,4]benzodioxino[2,3-c]pyridazine.
(2) 6-Chloro-3-(2-hydroxyphenoxy)-4-pyridazinol (Compound No. 384,
Step O-2)
A mixture comprising 5.52 g (25.0 mmol) of
3-chloro[1,4]benzodioxino[2,3-c]pyridazine obtained in (1), 1.30 g
(31.2 mmol) of 96% sodium hydroxide, dimethylsulfoxide (55 mL) and
water (15 mL) was stirred at 90.degree. C. for 1 hour. The reaction
mixture was poured into ice-cold water, made acidic with
hydrochloric acid, and extracted with ethyl acetate. The solvent
was removed, and the residue was washed with isopropyl ether to
obtain 4.90 g (20.5 mmol, Yield: 82.0%) of
6-chloro-3-(2-hydroxyphenoxy)-4-pyridazinol (Compound No. 384).
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.25-6.40 (5H, m).
Melting point (.degree. C.): 216-219.
EXAMPLE 11
6-Chloro-3-[2-(methylsulfinyl)phenoxy]-4-pyridazinol (Compound No.
404)
(1) 6-Chloro-3-[2-(methylsulfanyl)phenoxy]pyridazine 1-oxide (Step
B-2)
In a mixed solvent of 1,4-dioxane (5 mL) and dimethylsulfoxide (5
mL) was dissolved 454 mg (3.24 mmol) of 2-(methylsulfanyl)phenol,
to the solution was added 519 mg (4.63 mmol) of potassium
tert-butoxide and the mixture was stirred for 35 minutes. To the
mixture was added 424 mg (2.57 mmol) of 3,6-dichloropyridazine
1-oxide and the resulting mixture was stirred for 3 hours. The
reaction mixture was poured into water and extracted with ethyl
acetate. The organic layers were combined, washed with brine, and
dried over anhydrous magnesium sulfate. The solvent was removed,
and the obtained residue was purified by silica gel chromatography
(Wakogel C-100, eluted with hexane:ethyl acetate=3:1) to obtain 391
mg (1.46 mmol, Yield: 56.8%) of
6-chloro-3-[2-(methylsulfanyl)phenoxy]pyridazine 1-oxide.
(2) 4,6-Dichloro-3-[2-(methylsulfanyl)phenoxy]pyridazine (Step
B-3)
288 mg (1.07 mmol) of
6-chloro-3-[2-(methylsulfanyl)-phenoxy]pyridazine 1-oxide obtained
in (1) and 1.00 mL (10.8 mmol) of phosphorus oxychloride were
mixed, and the mixture was stirred overnight. The reaction mixture
was poured into water, and extracted with ethyl acetate. The
organic layer was washed successively with a saturated aqueous
sodium hydrogen carbonate solution and brine, and dried over
anhydrous magnesium sulfate. The solvent was distilled off and the
residue was purified by preparative thin-layer chromatography
(available from Merck Co., 1.05744, developed by hexane/ethyl
acetate=3/1) to obtain 118 mg (0.411 mmol, Yield: 38.4%) of
4,6-dichloro-3-[2-(methylsulfanyl)phenoxy]pyridazine.
(3) 4,6-Dichloro-3-[2-(methylsulfinyl)phenoxy]pyridazine
In 1,2-dichloroethane (4 mL) was dissolved 118 mg (0.411 mmol) of
4,6-dichloro-3-[2-(methylsulfanyl)phenoxy]pyridazine obtained in
(2), 96.3 mg (purity 80%, 0.446 mmol) of m-chloroperbenzoic acid
was added to the solution and the resulting mixture was stirred at
room temperature for 5 hours. The reaction mixture was poured into
10% aqueous sodium sulfite solution, extracted with ethyl acetate,
then washed with brine, and dried over anhydrous magnesium sulfate.
The solvent was distilled off and the obtained residue was purified
by preparative thin-layer chromatography (available from Merck Co.,
1.05744, developed by hexane:ethyl acetate=1:1, then, 3:1, and
then, 1:1) to obtain 21.1 mg (0.0696 mmol, Yield: 16.9%) of
4,6-dichloro-3-[2-(methylsulfinyl)phenoxy]pyridazine.
(4) 6-Chloro-3-[2-(methylsulfinyl)phenoxy]-4-pyridazinol (Compound
No. 404, Step B-4)
In 1,4-dioxane (0.5 mL) was dissolved 21.1 mg (0.0696 mmol) of
4,6-dichloro-3-[2-(methylsulfinyl)phenoxy]pyridazine obtained in
(3), 0.12 mL (0.36 mmol) of 3 mol/L aqueous sodium hydroxide
solution was added to the solution, and the resulting mixture was
stirred for 45 minutes. To the mixture was added dimethylsulfoxide
(0.5 mL), and after stirring for 3 hours, the reaction mixture was
poured into 10% hydrochloric acid and extracted with ethyl acetate.
The organic layer was successively washed with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was distilled
off and the obtained residue was purified by preparative thin-layer
chromatography (available from Merck Co., 1.05744,
chloroform:methanol=10:1) to obtain 2.1 mg (0.0074 mmol, Yield:
11%) of 6-chloro-3-[2-(methylsulfinyl)phenoxy]-4-pyridazinol
(Compound No. 404).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.90-7.84 (1H, m),
7.60-7.42 (2H, m), 7.14 (1H, dd, J=9.2, 1.1 Hz), 6.62 (1H, s), 2.92
(3H, s). Appearance: amorphous.
EXAMPLE 12
6-Chloro-3-[2-(methylsulfonyl)phenoxy]-4-pyridazinol (Compound No.
406)
(1) 6-Chloro-3-[2-(methylsulfonyl)phenoxy]pyridazine 1-oxide
In 1,2-dichloroethane (5 mL) was dissolved 208 mg (0.774 mmol) of
6-chloro-3-[2-(methylsulfanyl)phenoxy]pyridazine 1-oxide obtained
in Example 11 (1), 829 mg (3.84 mmol) of 80% m-chloroperbenzoic
acid was added to the solution and the resulting mixture was
stirred at room temperature for 4 hours. The reaction mixture was
poured into 10% aqueous sodium sulfite solution, and extracted with
ethyl acetate. The organic layers were combined, washed with brine
and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (available from Merck Co., 1.05744,
developed by hexane:ethyl acetate=1:1) to obtain 132 mg (0.439
mmol, Yield: 56.7%) of
6-chloro-3-[2-(methylsulfonyl)phenoxy]pyridazine 1-oxide.
(2) 4,6-Dichloro-3-[2-(methylsulfonyl)phenoxy]pyridazine (Step
B-3)
111 mg (0.369 mmol) of
6-chloro-3-[2-(methylsulfonyl)phenoxy]pyridazine 1-oxide obtained
in (1) and 1.00 mL (10.8 mmol) of phosphorus oxychloride were
mixed, and the mixture was stirred overnight. The reaction mixture
was poured into water, and extracted with ethyl acetate. The
organic layer was successively washed with a saturated sodium
hydrogen carbonate and brine, and dried over anhydrous magnesium
sulfate. The solvent was distilled off and the residue was purified
by preparative thin-layer chromatography (available from Merck Co.,
1.05744, developed by hexane:ethyl acetate=1:1) to obtain 70.8 mg
(0.222 mmol, Yield: 60.2%) of
4,6-dichloro-3-[2-(methylsulfonyl)phenoxy]pyridazine.
(3) 6-Chloro-3-[2-(methylsulfonyl)phenoxy]-4-pyridazinol (Compound
No. 406, Step B-4)
In 1,4-dioxane (2.0 mL) was dissolved 70.8 mg (0.222 mmol) of
4,6-dichloro-3-[2-(methylsulfonyl)phenoxy]pyridazine obtained in
(2), 0.45 mL (1.4 mmol) of 3 mol/L aqueous sodium hydroxide
solution was added to the solution, and the resulting mixture was
stirred for 30 minutes. To the mixture was added dimethylsulfoxide
(2.0 mL), the mixture was stirred overnight, poured into water and
washed with a mixed solvent of hexane-ethyl acetate. To the aqueous
layer was added 10% hydrochloric acid to make it acidic, and the
mixture was extracted with ethyl acetate. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from Merck Co., 1.05744, developed by
chloroform:methanol=10:1) to obtain 18.0 mg (0.0599 mmol, Yield:
27.0%) of 6-chloro-3-[2-(methylsulfonyl)phenoxy]-4-pyridazinol
(Compound No. 406).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.00 (1H, dd, J=7.7,
1.8 Hz), 7.71 (1H, ddd, J=7.7, 7.7, 1.8 Hz), 7.43 (1H, ddd, J=7.7,
7.7, 1.1 Hz), 7.32 (1H, br.d, J=7.7 Hz), 6.62 (1H, s), 3.36 (3H,
s). Appearance: amorphous.
EXAMPLE 13
6-Chloro-3-(2-cyclopropyl-3-methoxyphenoxy)-4-pyridazinol (Compound
No. 478)
(1)
6-Chloro-3-(2-cyclopropyl-3-methoxyphenoxy)-4-methoxy-pyridazine
(Step D-1)
In a mixed solvent of 1,4-dioxane (2.5 mL) and dimethylsulfoxide
(2.5 mL) was dissolved 190 mg (1.16 mmol) of
2-cyclopropyl-3-methoxyphenol, 146 mg (1.30 mmol) of potassium
tert-butoxide was added to the solution and the resulting mixture
was stirred for 10 minutes. To the mixture was added 170 mg (0.950
mmol) of 3,6-dichloro-4-methoxypyridazine and the resulting mixture
was stirred overnight. The reaction mixture was poured into ice
water and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was removed, and the
obtained residue was purified by silica gel chromatography (Wakogel
C-100, hexane-ethyl acetate, gradient) to obtain 90.1 mg (0.293
mmol, Yield: 30.8%) of
6-chloro-3-(2-cyclopropyl-3-methoxyphenoxy)-4-methoxypyridazine and
114 mg (0.371 mmol, Yield: 39.1%) of
3-chloro-6-(2-cyclopropyl-3-methoxyphenoxy)-4-methoxypyridazine.
(2) 6-Chloro-3-(2-cyclopropyl-3-methoxyphenoxy)-4-pyridazinol
(Compound No. 478, Step D-2)
In dry N,N-dimethylformamide (DMF, 2 mL) was suspended 24 mg (0.60
mmol) of 60% sodium hydride, 0.05 mL (0.7 mmol) of ethanethiol was
added dropwise to the suspension in an ice bath and the resulting
mixture was stirred at room temperature for 10 minutes. To the
mixture was added a dry N,N-dimethylformamide (DMF, 1.5 mL)
solution containing 60.0 mg (0.195 mmol,) of
6-chloro-3-(2-cyclopropyl-3-methoxyphenoxy)-4-methoxypyridazine
obtained in (1), and the resulting mixture was refluxed for 2
hours. The reaction mixture was cooled, and poured into ice-cold 1
mol/L aqueous sodium hydroxide solution, and washed with ethyl
acetate. Ice-cold conc. hydrochloric acid was added to the aqueous
layer to adjust pH to 4, and the mixture was extracted with ethyl
acetate. The ethyl acetate extracts were combined, washed
successively with water and brine, and dried over sodium sulfate.
The solvent was distilled off and the obtained residue was purified
by preparative thin-layer chromatography (available from Merck Co.,
1.05744, 3 plates were used, developed by hexane:ethyl acetate=1:1)
to obtain 15.2 mg (0.0519 mmol, Yield: 26.6%) of
6-chloro-3-(2-cyclopropyl-3-methoxyphenoxy)-4-pyridazinol (Compound
No. 478).
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.19 (1H, dd, J=8.1,
8.4 Hz), 6.76 (1H, d, J=8.1 Hz), 6.69 (1H, d, J=8.4 Hz), 6.60 (1H,
s), 3.85 (3H, s), 1.55-1.35 (1H, m), 0.85-0.60 (4H, m). Melting
point (.degree. C.): 184-185.
EXAMPLE 14
3-(1,1a,6,6a-Tetrahydrocyclopropa[a]inden-2-yloxy)-6-chloro-4-pyridazinol
(Compound No. 515)
(1) 7-hydroxy-1-indanone
37.0 g (278 mmol) of aluminum chloride was mixed with 3.70 g (61.3
mmol) of sodium chloride, the mixture was dissolved at 150.degree.
C. under heating, 6.40 g (43.2 mmol) of commercially available
2,3-dihydro-4H-chromen-4-one dissolved by heating (50.degree. C.)
was added to the mixture and the resulting mixture was stirred at
200.degree. C. for 20 minutes. The reaction mixture (gum state) was
cooled, and added to ice-cold hydrochloric acid (100 ml of conc.
hydrochloric acid and ice were combined to make them 200 ml) little
by little and stirred for 30 minutes. Methylene chloride was added
to the mixture and the mixture was separated. The aqueous layer was
filtered, and the filtrate was extracted with methylene chloride.
The organic layers were combined, washed successively with water
and brine, and dried over sodium sulfate. The solvent was removed,
and the obtained residue was purified by silica gel chromatography
(Wakogel C-100, hexane-ethyl acetate, gradient) to obtain 4.82 g
(32.6 mmol, Yield: 75.2%) of 7-hydroxy-1-indanone.
(2) 7-(Methoxymethoxy)-1-indanone
In N,N-dimethylformamide (DMF, 33 mL) was dissolved 1.00 g (6.76
mmol) of 7-hydroxy-1-indanone obtained in (1), the solution was
cooled in an ice bath, and 0.330 g (8.25 mmol) of 60% sodium
hydride was added by dividing into four times and the resulting
mixture was stirred for 30 minutes. To the mixture was added
dropwise 0.80 mL (11 mmol) of chloromethoxymethane, and the mixture
was stirred at room temperature for 2 hours. The reaction mixture
was poured into an ice-cold saturated aqueous ammonium chloride
solution (100 mL) and extracted with ethyl acetate. The organic
layer was washed successively with water and and brine, dried over
sodium sulfate. The solvent was removed, and the obtained residue
was purified by silica gel chromatography (Wakogel C-100,
hexane-ethyl acetate, gradient) to obtain 1.04 g (5.42 mmol, Yield:
80.2%) of 7-(methoxymethoxy)-1-indanone.
(3) 7-(Methoxymethoxy)-1-indanol
In methanol(20 mL) was dissolved 1.04 g (5.42 mmol) of
7-methoxymethoxy-1-indanone obtained in (2), the solution was
cooled in an ice bath, and 164 mg (4.34 mmol) of sodium borohydride
was added to the solution and the resulting mixture was stirred at
room temperature for 4 hours. The reaction mixture was poured into
ice water, and extracted with ethyl acetate. The organic layers
were combined, washed successively with water and brine, and dried
over sodium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel chromatography (Wakogel C-100,
hexane-ethyl acetate, gradient) to obtain 1.05 g (5.42 mmol, Yield:
100%) of 7-(methoxymethoxy)-1-indanol.
(4) Mixture of 4-(methoxymethoxy)-1H-indene and
7-(methoxymethoxy)-1H-indene
In methylene chloride (3 mL) was dissolved 500 mg (2.58 mmol) of
7-(methoxymethoxy)-1-indanol obtained in (3), the solution was
cooled in an ice bath, and 0.50 mL (3.7 mmol) of triethylamine and
0.25 mL (3.3 mmol) of methanesulfonyl chloride were added to the
solution and the resulting mixture was stirred for 2 hours. To the
mixture was added 0.80 mL (5.7 mmol) of triethylamine and the
mixture was stirred for 1 hour, then the mixture was poured into
water and extracted with methylene chloride. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the resulting
residue was dissolved in pyridine (3 mL), and the mixture was
refluxed for 4 hours. After allowing to stand at room temperature
overnight, the reaction mixture was poured into water and extracted
with ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the obtained residue was
purified by silica gel chromatography (Wakogel C-100, hexane-ethyl
acetate, gradient) to obtain 280 mg (1.59 mmol, Yield: 61.6%) of a
mixture of 4-(methoxymethoxy)-1H-indene and
7-(methoxymethoxy)-1H-indene.
(5) Mixture of
(2-(methoxymethoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]indene and
5-(methoxymethoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]indene
In 30 mL of eggplant type flask was charged dry diethyl ether (5
mL) under nitrogen atmosphere, and cooled in an ice bath. To the
solution were successively added dropwise 6.3 mL (6.3 mmol) of
diethylzinc (1.0 mol/L hexane solution), and 0.70 mL (8.5 mmol) of
diiodomethane, and the mixture was stirred for 10 minutes. To the
mixture was gradually added dropwise an ether solution (9 mL)
containing 250 mg (1.42 mmol) of a mixture comprising
4-(methoxymethoxy)-1H-indene and 7-(methoxymethoxy)-1H-indene
obtained in (4). The resulting mixture was refluxed for 4 hours.
The reaction mixture was cooled, and poured into a saturated
aqueous ammonium chloride solution. To the mixture was added the
same volume of a saturated aqueous sodium hydrogen carbonate
solution, and then, extracted with ether. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was removed, and the
obtained residue was purified by silica gel chromatography (Wakogel
C-100, hexane-ethyl acetate, gradient) to obtain 150 mg (0.789
mmol, Yield: 55.6%) of a mixture of
2-(methoxymethoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]indene and
5-(methoxymethoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]-indene.
(6) Mixture of 1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-ol and
1,1a,6,6a-tetrahydrocyclopropa[a]inden-5-ol
In methanol (6 mL) was dissolved 150 mg (0.789 mmol) of a mixture
of 2-(methoxymethoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]indene and
5-(methoxymethoxy)-1,1a,6,6a-tetrahydrocyclopropa[a]indene obtained
in (5), two drops of conc. hydrochloric acid were added to the
solution and the resulting mixture was stirred at room temperature
for 1 hour and then at 60.degree. C. for 20 minutes. The reaction
mixture was cooled, poured into water and extracted with ethyl
acetate. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous sodium sulfate. The
solvent was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from Merck Co.,
1.05744, developed by hexane:ethyl acetate=2:1) to obtain 80.0 mg
(0.548 mmol, Yield: 69.5%) of a mixture of
1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-ol and
1,1a,6,6a-tetrahydrocyclopropa[a]inden-5-ol.
(7) Mixture of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-yloxy)-6-chloropyridazine
1-oxide and
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-5-yloxy)-6-chloropyridazine
1-oxide (Step B-2)
In a mixed solvent of 1,4-dioxane (2 mL) and dimethylsulfoxide (2
mL) was dissolved 80.0 mg (0.548 mmol) of a mixture of
1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-ol and
1,1a,6,6a-tetrahydrocyclopropa[a]inden-5-ol obtained in (6), and 85
mg (0.76 mmol) of potassium tert-butoxide was added to the solution
and the mixture was stirred for 10 minutes. To the mixture was
added 82 mg (0.50 mmol) of 3,6-dichloropyridazine 1-oxide, and the
resulting mixture was stirred at room temperature overnight. The
reaction mixture was poured into water and extracted with ethyl
acetate. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from Merck Co.,
1.05744, 4 plates were used, developed by hexane:ethyl acetate=2:1)
to obtain 75.0 mg (0.273 mmol, Yield: 49.8%) of a mixture of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-yloxy)-6-chloropyridazine
1-oxide and
3-(1,1a,6,6a-tetrahydrocyclopropa-[a]inden-5-yloxy)-6-chloropyridazine
1-oxide.
(8)
3-(1,1a,6,6a-Tetrahydrocyclopropa[a]inden-2-yloxy)-4,6-dichloropyridaz-
ine and
3-(1,1a,6,6a-tetrahydrocyclopropa-[a]inden-5-yloxy)-4,6-dichloropy-
ridazine (Step B-3)
75.0 mg (0.273 mmol) of a mixture of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-yloxy)-6-chloropyridazine
1-oxide and
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-5-yloxy)-6-chloropyridazine
1-oxide obtained in (7) was mixed with 0.30 mL (3.2 mmol) of
phosphorus oxychloride, and the mixture was stirred overnight. The
reaction mixture was concentrated under reduced pressure to remove
phosphorus oxychloride, and the residue was purified by preparative
thin-layer chromatography (available from Merck Co., 1.05744, 3
plates were used, developed by hexane/ethyl acetate=9/1 four times
repeatedly) to obtain 21.4 mg (0.0730 mmol, Yield: 26.7%) of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-yloxy)-4,6-dichloropyridazine
and 32.6 mg (0.111 mmol, Yield: 40.7%) of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-5-yloxy)-4,6-dichloropyridazine-
.
(9)
3-(1,1a,6,6a-Tetrahydrocyclopropa[a]inden-2-yloxy)-6-chloro-4-pyridazi-
nol (Compound No. 515, Step B-4)
To a dimethylsulfoxide (3 mL) solution containing 21.4 mg (0.0730
mmol) of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-yloxy)-4,6-dichloropyridaz-
ine obtained in (8) was added 0.1 mL (0.2 mmol) of 2 mol/L aqueous
sodium hydroxide solution, and the mixture was stirred at room
temperature for 3 hours. The reaction mixture was poured into
ice-cold 1 mol/L aqueous sodium hydroxide solution, and extracted
with ethyl acetate. The aqueous layer was separated, conc.
hydrochloric acid was added thereto to adjust pH to 4 in an ice
bath, and the mixture was extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine,
dried over sodium sulfate. The solvent was distilled off and the
obtained residue was purified by preparative thin-layer
chromatography (available from Merck Co., 1.05744, 1 plate was
used, developed by chloroform:methanol=10:1) to obtain 10.3 mg
(0.0375 mmol, Yield: 51.4%) of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-2-yloxy)-6-chloro-4-pyridazi-
nol (Compound No. 515).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.08 (1H, t, J=7.7
Hz), 6.98 (1H, d, J=7.7 Hz), 6.84 (1H, d, J=7.7 Hz), 6.59 (1H, s),
3.20 (1H, dd, J=17.2, 6.2 Hz), 2.94 (1H, d, J=17.2 Hz), 2.30-2.15
(1H, m), 1.90-1.75 (1H, m), 1.05-0.90 (1H, m). Melting point
(.degree. C.): 245-247.
EXAMPLE 15
3-(1,1a,6,6a-Tetrahydrocyclopropa[a]inden-5-yloxy)-6-chloro-4-pyridazinol
(Compound No. 516, Step B-4)
In dimethylsulfoxide (3 mL) was dissolved 32.6 mg (0.111 mmol) of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-5-yloxy)-4,6-dichloropyridazine
obtained in Example 14(8), and 0.1 mL (0.2 mmol) of 2 mol/L aqueous
sodium hydroxide solution was added to the solution and the
resulting mixture was stirred at room temperature for 4 hours. The
reaction mixture was poured into ice-cold 1 mol/L aqueous sodium
hydroxide solution, and washed with ethyl acetate. The aqueous
layer was separated, conc. hydrochloric acid was added thereto to
adjust pH to 4 in an ice bath, and extracted with ethyl acetate.
The organic layers were combined, washed successively with water
and brine, dried over sodium sulfate. The solvent was distilled off
and the obtained residue was purified by preparative thin-layer
chromatography (available from Merck Co., 1.05744, 1 plate was
used, developed by chloroform:methanol=10:1) to obtain 13.4 mg
(0.0487 mmol, Yield: 43.9%) of
3-(1,1a,6,6a-tetrahydrocyclopropa[a]inden-5-yloxy)-6-chloro-4-pyridazinol
(Compound No. 516).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.25-7.05 (2H, m),
6.83 (1H, dd, J=6.6, 2.6 Hz), 6.67 (1H, s), 3.00 (1H, dd, J=17.2,
6.6 Hz), 2.78 (1H, d, J=17.2 Hz), 2.50-2.35 (1H, m), 2.00-1.80 (1H,
m), 1.15-1.00 (1H, m), 0.10-0.00 (1H, m). Melting point (.degree.
C.): 211-213.
EXAMPLE 16
6-Chloro-3-(2-methoxy-5-methylphenoxy)-4-pyridazinol (Compound No.
704)
(1) 6-Chloro-3-(2-methoxy-5-methylphenoxy)pyridazine 1-oxide (Step
B-2)
In a mixed solvent of 1,4-dioxane (3 mL) and dimethylsulfoxide (3
mL) was dissolved 167.5 mg (1.21 mmol) of commercially available
2-methoxy-5-methylphenol, and 142.8 mg (1.27 mmol) of potassium
tert-butoxide was added to the solution, then 202.9 mg (1.23 mmol)
of 3,6-dichloropyridazine 1-oxide was added to the mixture and the
resulting mixture was stirred at room temperature overnight. The
reaction mixture was poured into water, and extracted with ethyl
acetate. The organic layer was successively washed with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 3
plates were used, developed by ethyl acetate:hexane=2:1) to obtain
226.5 mg (0.849 mmol, Yield: 70.2%) of
6-chloro-3-(2-methoxy-5-methylphenoxy)pyridazine 1-oxide.
(2) 4,6-Dichloro-3-(2-methoxy-5-methylphenoxy)pyridazine (Step
B-3)
In phosphorus oxychloride (1 mL) was dissolved 226.5 mg (0.849
mmol) of 6-chloro-3-(2-methoxy-5-methylphenoxy)-pyridazine 1-oxide
obtained in (1), and the solution was stirred at room temperature
overnight. To the reaction mixture were added water and methylene
chloride, and after stirring for 30 minutes, it was extracted with
methylene chloride. The organic layer was successively washed with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 3 plates were used, developed by ethyl acetate:hexane=2:1)
to obtain 205.3 mg (0.720 mmol, Yield: 84.8%) of
4,6-dichloro-3-(2-methoxy-5-methylphenoxy)pyridazine.
(3) 6-Chloro-3-(2-methoxy-5-methylphenoxy)-4-pyridazinol (Compound
No. 704, Step B-4)
In a mixed solvent of 1,4-dioxane (5 mL) and dimethylsulfoxide (5
mL) was dissolved 205.3 mg (0.720 mmol) of
4,6-dichloro-3-(2-methoxy-5-methylphenoxy)pyridazine obtained in
(2), and 1.8 mL (3.6 mmol) of 2 mol/L aqueous sodium hydroxide
solution was added to the solution, and the resulting mixture was
stirred at room temperature overnight. Water was added to the
reaction mixture, diluted hydrochloric acid was added thereto to
adjust pH to 2, and the mixture was extracted with ethyl acetate.
The organic layer was successively washed with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was distilled
off and the obtained residue was purified by preparative thin-layer
chromatography (available from MERCK CO., 1.05744, 3 plates were
used, developed by ethyl acetate) to obtain 148.1 mg (0.555 mmol,
Yield: 77.1%) of
6-chloro-3-(2-methoxy-5-methylphenoxy)-4-pyridazinol (Compound No.
704).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.04-6.91 (3H, m),
6.66 (1H, s), 3.70 (3H, s), 2.27 (3H, s). Melting point (.degree.
C.): 126-134.
EXAMPLE 17
6-Chloro-3-{2-[1-(ethylsulfanyl)ethyl]-6-fluorophenoxy}-4-pyridazinol
(Compound No. 728)
(1) 3-Fluoro-2-methoxybenzaldehyde
To an acetonitrile (50 mL) solution containing 3.01 g (21.5 mmol)
of commercially available 3-fluoro-2-hydroxybenzaldehyde were added
5.92 g (42.8 mmol) of potassium carbonate and 6.66 mL (107 mmol) of
methyl iodide, and the mixture was stirred at 90.degree. C. for 3
hours. After allowing to stand at room temperature overnight, the
reaction mixture was poured into water, and extracted with ethyl
acetate. The organic layer was successively washed with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
removed, and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate, gradient) to
obtain 3.22 g of a crude product of
3-fluoro-2-methoxybenzaldehyde.
(2) 1-Fluoro-2-methoxy-3-vinylbenzene
Under nitrogen atmosphere, 273.2 mg (6.83 mmol) of 60% sodium
hydride washed with hexane was suspended in dry dimethylsulfoxide
(3 mL), and the suspension was stirred at 85.degree. C. for 30
minutes, cooled to room temperature and then, in an ice bath, a dry
dimethylsulfoxide (8 mL) solution containing 2.44 g (6.83 mmol) of
methyl(triphenyl)phosphonium bromide was gradually added dropwise.
After stirring at room temperature for 30 minutes, a dry
dimethylsulfoxide (5 mL) solution containing 877.4 mg of a crude
product of 3-fluoro-2-methoxybenzaldehyde obtained in (1) was added
dropwise, and the mixture was stirred at room temperature for 30
minutes. The reaction mixture was poured into water, and extracted
with ethyl acetate. The organic layer was washed successively with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was removed, and the obtained residue was purified by
silica gel column chromatography (Wako gel C-100, hexane-ethyl
acetate, gradient) to obtain 0.38 g (2.5 mmol) of
1-fluoro-2-methoxy-3-vinylbenzene.
(3) 1-Cyclopropyl-3-fluoro-2-methoxybenzene
Under nitrogen atmosphere, dry diethyl ether (5 mL) was charged in
a dry flask, 9.20 mL (9.20 mmol) of diethyl-zinc (1 mol/L hexane
solution) was then added dropwise, and a dry diethyl ether (10 mL)
solution containing 0.56 g (3.7 mmol) of
1-fluoro-2-methoxy-3-vinylbenzene obtained in (2) was added
dropwise thereto. After stirring at room temperature for 5 minutes,
1.48 mL (18.4 mmol) of diiodomethane was added dropwise thereto,
and the resulting mixture was refluxed for 5 hours. After cooling
to room temperature, 9.20 mL (9.20 mmol) of diethylzinc (1 mol/L
hexane solution) and 1.48 mL (18.4 mmol) of diiodomethane were
additionally added, and the resulting mixture was again refluxed
for 4 hours. After allowing to stand at room temperature overnight,
the reaction mixture was poured into a saturated aqueous ammonium
chloride solution. To the mixture was added a saturated aqueous
sodium hydrogen carbonate solution and after stirring for 30
minutes, and the mixture was extracted with diethyl ether. The
organic layer was successively washed with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was removed,
and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate, gradient) to
obtain 0.82 g of a crude product of
1-cyclopropyl-3-fluoro-2-methoxybenzene.
(4)
6-Chloro-3-{2-[1-(ethylsulfanyl)ethyl]-6-fluorophenoxy}pyridazine
1-oxide (Step B-2)
Under nitrogen atmosphere, 288.8 mg (7.22 mmol) of 60% sodium
hydride was suspended in dry N,N-dimethylformamide (3 mL), and 0.55
mL (7.5 mmol) of ethanethiol was gradually added dropwise to the
suspension. After stirring for 15 minutes, a dry
N,N-dimethylformamide (6 mL) solution containing 402.1 mg of a
crude product of 1-cyclopropyl-3-fluoro-2-methoxybenzene obtained
in (3) was added dropwise thereto, and the resulting mixture was
stirred at 160.degree. C. for 5 hours. After allowing to stand at
room temperature overnight, 1 mol/L aqueous potassium hydroxide
solution and diethyl ether were added to the reaction mixture. The
aqueous layer was separated, washed with diethyl ether, and added
thereto diluted hydrochloric acid to adjust pH to 2. The mixture
was extracted with diethyl ether, ether extracts were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 3 plates were used, developed
by ethyl acetate:hexane=4:1) to obtain 299.9 mg of a mixture.
In a mixed solvent of 1,4-dioxane (3 mL) and dimethylsulfoxide (3
mL) was dissolved 152.7 mg of the mixture, 116.1 mg (1.03 mmol) of
potassium tert-butoxide was added to the solution, then 162.6 mg
(0.988 mmol) of 3,6-dichloropyridazine 1-oxide was added thereto,
and the resulting mixture was stirred at room temperature
over-night. The reaction mixture was poured into water, and
extracted with ethyl acetate. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was distilled off and the obtained residue was
purified by preparative thin-layer chromatography (available from
MERCK CO., 1.05744, 3 plates were used, developed by ethyl
acetate:hexane=2:1) to obtain 46.6 mg (0.144 mmol) of
6-chloro-3-{2-[1-(ethylsulfanyl)ethyl]-6-fluorophenoxy}pyridazine
1-oxide.
(5)
4,6-Dichloro-3-{2-[1-(ethylsulfanyl)ethyl]-6-fluorophenoxy}pyridazine
(Step B-3)
A phosphorus oxychloride (0.5 mL) solution containing 46.6 mg
(0.144 mmol) of
6-chloro-3-{2-[1-(ethylsulfanyl)-ethyl]-6-fluorophenoxy}pyridazi-
ne 1-oxide obtained in (4) was stirred at room temperature
overnight. The reaction mixture was poured into water, and
extracted with ethyl acetate. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was distilled off and the obtained residue was
purified by preparative thin-layer chromatography (available from
MERCK CO., 1.05744, 1 plate was used, developed by ethyl
acetate:hexane=4:1) to obtain 9.8 mg (0.028 mmol, Yield: 19%) of
4,6-dichloro-3-{2-[1-(ethylsulfanyl)ethyl]-6-fluorophenoxy}pyridazine.
(6)
6-Chloro-3-{2-[1-(ethylsulfanyl)ethyl]-6-fluorophenoxy}-4-pyridazinol
(Compound No. 728, Step B-4)
In a mixed solvent of 1,4-dioxane (1 mL) and dimethylsulfoxide (1
mL) was dissolved 9.8 mg (0.028 mmol) of
4,6-dichloro-3-{2-[l-(ethylsulfanyl)ethyl]-6-fluorophenoxy}pyridazine
obtained in (5), 0.07 mL (0.14 mmol) of 2 mol/L aqueous sodium
hydroxide solution was added to the solution, and the resulting
mixture was stirred at room temperature overnight. The reaction
mixture was poured into water, diluted hydrochloric acid was added
thereto to adjust pH to 2, and the mixture was extracted with ethyl
acetate. The organic layer was successively washed with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 1
plate was used, developed by ethyl acetate) to obtain 2.2 mg
(0.0067 mmol, Yield: 24%) of
6-chloro-3-{2-[1-(ethylsulfanyl)ethyl]-6-fluorophenoxy}-4-pyridazinol
(Compound No. 728).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.42 (1H, d, J=8.1
Hz), 7.26-7.15 (1H, m), 7.07-6.97 (1H, m), 6.46 (1H, s), 4.33 (1H,
q, J=7.0 Hz), 2.42-2.20 (2H, m), 1.43 (3H, d, J=7.0 Hz), 1.02 (3H,
t, J=7.0 Hz). Appearance: amorphous.
EXAMPLE 18
6-Chloro-3-(2-chloro-6-isopropylphenoxy)-4-pyridazinol (Compound
No. 738)
(1) 1-Isopropyl-2-[(2-methoxyethoxy)methoxy]benzene
In dry tetrahydrofuran (60 mL) was suspended 4.80 g (120 mmol) of
60% sodium hydride, and a dry tetrahydrofuran (80 mL) solution
containing 13.6 g (100 mmol) of 2-isopropylphenol was added
dropwise to the suspension at 0.degree. C. After stirring at
0.degree. C. for 10 minutes, a dry tetrahydrofuran (80 mL) solution
containing 14.9 g (119 mmol) of 2-methoxyethoxymethyl chloride was
added dropwise thereto. The reaction mixture was stirred in an ice
bath for 2 hours, poured into ice-cold water (250 mL), and
extracted with ethyl acetate. The organic layers were combined,
washed succeccively with 1 mol/L aqueous sodium hydroxide solution
and brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (eluted with hexane:ethyl acetate=50:1) to obtain
18.1 g (80.8 mmol, Yield: 80.8%) of
1-isopropyl-2-[(2-methoxyethoxy)methoxy]benzene.
(2) 1-Chloro-3-isopropyl-2-[(2-methoxyethoxy)methoxy]-benzene
In a dry ether (100 mL) was dissolved 8.00 g (35.7 mmol) of
1-isopropyl-2-[(2-methoxyethoxy)methoxy]benzene obtained in (1),
and 34.4 mL (55.0 mmol) of n-butyl lithium-hexane solution (1.60M)
was added to the solution in an ice bath (reaction solution
temperature: 5-10.degree. C.), and the mixture was stirred in an
ice bath for 5 hours. To the mixture was passed through 2.51 g
(35.4 mmol) of a chlorine gas while keeping the reaction solution
temperature to 5-10.degree. C. The reaction mixture was stirred in
an ice bath for 1 hour, poured into 1 mol/L hydrochloric acid (300
mL), and extracted with ether. The organic layers were combined,
dried over anhydrous sodium sulfate, and the solvent was removed.
The residue was purified by silica gel column chromatography
(eluted with hexane:ethyl acetate=100:1) to obtain 4.38 g (16.9
mmol, Yield: 47.3%) of
1-chloro-3-isopropyl-2-[(2-methoxyethoxy)methoxy]benzene.
(3) 2-Chloro-6-isopropylphenol
In dichloromethane (15 mL) was dissolved 4.38 g (16.9 mmol) of
1-chloro-3-isopropyl-2-[(2-methoxyethoxy)methoxy]-benzene obtained
in (2), 2.70 g (23.7 mmol) of trifluoroacetic acid was added to the
solution, and the resulting mixture was stirred at room temperature
overnight. The reaction mixture was poured into 1 mol/L
hydrochloric acid, and extracted with ethyl acetate. The organic
layers were combined, and dried over anhydrous sodium sulfate. The
solvent was removed, and the residue was purified by silica gel
column chromatography (eluted with hexane) to obtain 2.50 g (14.7
mmol, Yield: 87.0%) of 2-chloro-6-isopropylphenol.
(4) 3-Chloro-6-(2-chloro-6-isopropylphenoxy)pyridazine (Step
A-1)
1.98 g (17.7 mmol) of potassium tert-butoxide, 1,4-dioxane (100 mL)
and 2.50 g (14.7 mmol) of 2-chloro-6-isopropylphenol obtained in
(3) were mixed, and the mixture was stirred at room temperature for
20 minutes. To the mixture was added 2.18 g (14.6 mmol) of
3,6-dichloropyridazine and the mixture was refluxed for 4 hours. To
the reaction mixture was further added 0.50 g (4.5 mmol) of
potassium tert-butoxide, and the mixture was refluxed for further 3
hours. The reaction mixture was allowed to stand for cooling,
poured into 1N hydrochloric acid (100 mL), and extracted with ethyl
acetate. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous sodium sulfate. The
solvent was removed, and the obtained residue was purified by
silica gel column chromatography (hexane:ethyl acetate, gradient)
to obtain 3.18 g (11.2 mmol, Yield: 76.2%) of
3-chloro-6-(2-chloro-6-isopropylphenoxy)pyridazine.
(5) Mixture of 6-chloro-3-(2-chloro-6-isopropylphenoxy)-pyridazine
1-oxide and 3-chloro-6-(2-chloro-6-isopropylphenoxy)pyridazine
1-oxide (Step C-1)
In dry dichloromethane (90 mL) was dissolved 3.17 g (11.2 mmol) of
3-chloro-6-(2-chloro-6-isopropylphenoxy)-pyridazine obtained in
(4), 2.90 g (13.4-14.3 mmol) of 80-85% m-chloroperbenzoic acid was
added to the solution, and the mixture was refluxed for 13 hours.
The reaction mixture was poured into 1N aqueous sodium hydroxide
solution, and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous sodium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography
(hexane:ethyl acetate, gradient) to obtain 2.82 g (9.43 mmol,
Yield: 84.2%) of a mixture of
6-chloro-3-(2-chloro-6-isopropylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-chloro-6-isopropylphenoxy)pyridazine 1-oxide.
(6) Mixture of
4,6-dichloro-3-(2-chloro-6-isopropylphenoxy)pyridazine and
3,4-dichloro-6-(2-chloro-6-isopropylphenoxy)pyridazine (Step
C-2)
2.80 g (9.36 mmol) of a mixture of
6-chloro-3-(2-chloro-6-isopropylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-chloro-6-isopropylphenoxy)pyridazine 1-oxide obtained
in (5) was mixed with 17.5 mL (189 mmol) of phosphorus oxychloride,
and the mixture was refluxed for 2 hours and 30 minutes. The
reaction mixture was allowed to stand for cooling, poured into
ice-cold water, and extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine, and
dried over anhydrous sodium sulfate. The solvent was removed, and
the obtained residue was purified by silica gel column
chromatography (hexane:ethyl acetate=20:1) to obtain 0.850 g (2.67
mmol, m.p. 90-91.degree. C.) of
4,6-dichloro-3-(2-chloro-6-isopropylphenoxy)pyridazine, and 1.78 g
(5.60 mmol) of a mixture of
4,6-dichloro-3-(2-chloro-6-isopropylphenoxy)pyridazine and
3,4-dichloro-6-(2-chloro-6-isopropylphenoxy)pyridazine.
(7) 6-Chloro-3-(2-chloro-6-isopropylphenoxy)-4-methoxypyridazine
and 3-chloro-6-(2-chloro-6-isopropylphenoxy)-4-methoxypyridazine
(Step C-3)
To methanol (10 mL) was added 0.080 g (3.5 mmol) of sodium, and the
mixture was stirred at room temperature for 30 minutes. To the
mixture was added 0.830 g (2.61 mmol) of
4,6-dichloro-3-(2-chloro-6-isopropylphenoxy)pyridazine obtained in
(6), and the mixture was stirred at room temperature for 2 hours.
The reaction mixture was poured into ice-cold water, and extracted
with ethyl acetate. The organic layers were combined, dried over
anhydrous sodium sulfate, and the solvent was removed. The obtained
residue was purified by silica gel column chromatography (hexane:
ethyl acetate=10:1), washed with hexane and crystallized to obtain
0.720 g (2.30 mmol, Yield: 88.1%) of
6-chloro-3-(2-chloro-6-isopropylphenoxy)-4-methoxypyridazine. On
the other hand, 1.78 g (5.60 mmol) of the mixture of
4,6-dichloro-3-(2-chloro-6-isopropylphenoxy)pyridazine and
3,4-dichloro-6-(2-chloro-6-isopropylphenoxy)pyridazine was reacted
in the same manner as mentioned above to obtain 1.25 g (3.99 mmol,
Yield: 71.3%) of
6-chloro-3-(2-chloro-6-isopropylphenoxy)-4-methoxypyridazine and
0.300 g (0.958 mmol, Yield: 17.1%) of
3-chloro-6-(2-chloro-6-isopropylphenoxy)-4-methoxypyridazine.
(8) 6-Chloro-3-(2-chloro-6-isopropylphenoxy)-4-pyridazinol
(Compound No. 738, Step C-4)
In dimethylsulfoxide (13 mL) was dissolved 1.46 g (4.66 mmol) of
6-chloro-3-(2-chloro-6-isopropylphenoxy)-4-methoxypyridazine
obtained in (7), 3 mL (6.0 mmol) of 2 mol/L aqueous sodium
hydroxide solution was added to the solution, and the resulting
mixture was stirred at 80.degree. C. for 3 hours. The reaction
mixture was poured into water, and made acidic with hydrochloric
acid. The precipitated solid was collected by filtration, washed
with water, and air dried.
6-Chloro-3-(2-chloro-6-isopropylphenoxy)-4-pyridazinol (Compound
No. 738) was obtained in an amount of 1.33 g (4.45 mmol, Yield:
95.5%).
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 7.40-7.05 (3H, m),
6.70 (1H, s), 2.98 (1H, septet, J=6.2 Hz), 1.13 (6H, d, J=6.2 Hz).
Melting point (.degree. C.): 218-233.
EXAMPLE 19
3-(2-Bromo-6-isopropylphenoxy)-6-chloro-4-pyridazinol (Compound No.
760)
(1) 1-Bromo-3-isopropyl-2-[(2-methoxyethoxy)methoxy]benzene
In dry ether (100 mL) was dissolved 5.18 g (23.1 mmol) of
1-isopropyl-2-[(2-methoxyethoxy)methoxy]benzene obtained in Example
18(1), 22.3 mL (35.7 mmol) of n-butyl lithium-hexane solution
(1.60M) was added dropwise to the solution in an ice bath (reaction
solution temperature: 5-10.degree. C.), and the mixture was stirred
in an ice bath for 5 hours. To the reaction mixture was added 8.20
g (69.7 mmol) of 90% cyanogen bromide while maintaining the
reaction solution temperature to 5-10.degree. C. The reaction
mixture was stirred in an ice bath for 2 hours, poured into
ice-cold water (300 mL), and extracted with ether. The organic
layers were combined, dried over anhydrous sodium sulfate, and the
solvent was removed. The residue was purified by silica gel column
chromatography (eluted with hexane:ethyl acetate=100:1) to obtain
3.40 g (11.2 mmol, Yield: 48.5%) of
1-bromo-3-isopropyl-2-[(2-methoxyethoxy)-methoxy]benzene.
(2) 2-Bromo-6-isopropylphenol
In dichloromethane (10 mL) was dissolved 3.40 g (11.2 mmol) of
1-bromo-3-isopropyl-2-[(2-methoxyethoxy)methoxy]-benzene obtained
in (1), 2.50 g (21.9 mmol) of trifluoroacetic acid was added to the
solution, and the mixture was stirred at room temperature
overnight. The reaction mixture was poured into 1 mol/L
hydrochloric acid, and extracted with ethyl acetate. The organic
layers were combined, and dried over anhydrous sodium sulfate. The
solvent was removed, and the residue was purified by silica gel
column chromatography (eluted with hexane) to obtain 2.27 g (10.6
mmol, Yield: 94.6%) of 2-bromo-6-isopropylphenol.
(3) 3-(2-Bromo-6-isopropylphenoxy)-6-chloropyridazine (Step
A-1)
1.52 g (13.6 mmol) of potassium tert-butoxide, 1,4-dioxane (60 mL)
and 2.27 g (10.6 mmol) of 2-bromo-6-isopropylphenol obtained in (2)
were mixed, and the mixture was stirred at room temperature for 20
minutes. To the mixture was added 1.58 g (10.6 mmol) of
3,6-dichloropyridazine, and the resulting mixture was refluxed for
7 hours and 20 minutes. The reaction mixture was allowed to stand
for cooling, poured into ice-cold water (110 mL), and extracted
with ethyl acetate. The organic layers were combined, washed with
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, the obtained residue was recrystallized (from isopropyl
ether), then, purified by silica gel column chromatography
(hexane:ethyl acetate, gradient) to obtain 2.68 g (8.17 mmol,
Yield: 77.1%) of
3-(2-bromo-6-isopropylphenoxy)-6-chloropyridazine.
(4) Mixture of 3-(2-bromo-6-isopropylphenoxy)-6-chloropyridazine
1-oxide and 6-(2-bromo-6-isopropylphenoxy)-3-chloropyridazine
1-oxide (Step C-1)
In dry dichloromethane (35 mL) was dissolved 2.68 g (8.17 mmol) of
3-(2-bromo-6-isopropylphenoxy)-6-chloropyridazine obtained in (3),
2.12 g (9.80-10.4 mmol) of 80-85% m-chloroperbenzoic acid was added
to the solution, and the mixture was refluxed for 12 hours and 30
minutes. The reaction mixture was poured into 1 mol/L aqueous
sodium hydroxide solution, and extracted with ethyl acetate. The
organic layers were combined, washed with brine, and dried over
anhydrous sodium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography
(hexane:ethyl acetate=5:1) to obtain 2.26 g (6.57 mmol, Yield:
80.4%) of a mixture of
3-(2-bromo-6-isopropylphenoxy)-6-chloropyridazine 1-oxide and
6-(2-bromo-6-isopropylphenoxy)-3-chloropyridazine 1-oxide.
(5) Mixture of
3-(2-bromo-6-isopropylphenoxy)-4,6-dichloropyridazine and
6-(2-bromo-6-isopropylphenoxy)-3,4-dichloropyridazine (Step
C-2)
A mixture of 2.14 g (6.22 mmol) of
3-(2-bromo-6-isopropylphenoxy)-6-chloropyridazine 1-oxide and
6-(2-bromo-6-isopropylphenoxy)-3-chloropyridazine 1-oxide obtained
in (4) was mixed with 11.6 mL (125 mmol) of phosphorus oxychloride,
and the resulting mixture was refluxed for 3 hours. The reaction
mixture was cooled by allowing to stand, poured into ice-cold
water, and extracted with ethyl acetate. The organic layers were
combined, washed successively with 1 mol/L of an aqueous sodium
hydroxide solution, water and brine, and dried over anhydrous
sodium sulfate. The solvent was removed, and the obtained residue
was purified by silica gel column chromatography (hexane:ethyl
acetate=20:1) to obtain 2.22 g (6.13 mmol, Yield: 98.6%) of a
mixture of 3-(2-bromo-6-isopropylphenoxy)-4,6-dichloropyridazine
and 6-(2-bromo-6-isopropylphenoxy)-3,4-dichloropyridazine.
(6) 3-(2-Bromo-6-isopropylphenoxy)-6-chloro-4-methoxypyridazine
(Step-C-3)
To methanol (20 mL) was added 0.180 g (7.8 mmol) of sodium, and the
mixture was stirred at room temperature for 30 minutes. To the
mixture was added 2.22 g (6.13 mmol) of a mixture of
3-(2-bromo-6-isopropylphenoxy)-4,6-dichloropyridazine and
6-(2-bromo-6-isopropylphenoxy)-3,4-dichloropyridazine obtained in
(5) and the resulting mixture was stirred at room temperature for 4
hours. The reaction mixture was poured into ice-cold water, and
extracted with ethyl acetate. The organic layers were combined,
washed with brine, and dried over anhydrous sodium sulfate. The
solvent was removed, and the obtained residue was purified by
silica gel column chromatography (hexane:ethyl acetate=15:1), and
washed with hexane to crystallize to obtain 1.48 g (4.13 mmol,
Yield: 67.4%) of
3-(2-bromo-6-isopropylphenoxy)-6-chloro-4-methoxypyridazine. Also,
0.21 g (0.59 mmol, Yield: 9.6%) of
6-(2-bromo-6-isopropylphenoxy)-3-chloro-4-methoxypyridazine was
simultaneously obtained.
(7) 3-(2-Bromo-6-isopropylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 760, Step C-4)
In dimethylsulfoxide (10 mL) was dissolved 0.72 g (2.0 mmol) of
3-(2-bromo-6-isopropylphenoxy)-6-chloro-4-methoxypyridazine
obtained in (6), an aqueous sodium hydroxide solution (prepared by
dissolving 100 mg of sodium hydroxide in 1.5 mL of water, 2.4 mmol)
was added to the solution, and the resulting mixture was stirred at
80.degree. C. for 3 hours. The reaction mixture was poured into
water, and made acidic by hydrochloric acid. The precipitated solid
was collected by filtration, washed with water, and air-dried.
Thus, 0.56 g (1.6 mmol, Yield: 80%) of
3-(2-bromo-6-isopropylphenoxy)-6-chloro-4-pyridazinol (Compound No.
760) was obtained.
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.70-7.00 (3H, m),
6.89 (1H, s), 2.94 (1H, septet, J=7.0 Hz), 1.16 (6H, d, J=7.0 Hz).
Melting point (.degree. C.): 232-253 (dec.).
EXAMPLE 20
3-(2-Bromo-6-tert-butylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 761)
(1) tert-Butyl-2-[(2-methoxyethoxy)methoxy]benzene
In dry tetrahydrofuran (25 mL) was suspended 4.80 g (120 mmol) of
60% sodium hydride, and a dry tetrahydrofuran (80 mL) solution
containing 15.0 g (100 mmol) of 2-tert-butylphenol was added
dropwise to this suspension at 0.degree. C. After stirring the
mixture at 0.degree. C. for 10 minutes, a dry tetrahydrofuran (80
mL) solution containing 14.9 g (119 mmol) of 2-methoxyethoxymethyl
chloride was added dropwise to the mixture. The reaction mixture
was stirred in an ice bath for 4 hours and 30 minutes, and allowed
to stand at room temperature overnight. To the reaction mixture
were further added 1.20 g (30 mmol) of 60% sodium hydride and 3.8 g
(30 mmol) of 2-methoxyethoxymethyl chloride at 0.degree. C., and
the mixture was stirred at 0.degree. C. for 7 hours. The reaction
mixture was poured into ice-cold water (250 mL), and extracted with
ethyl acetate. The organic layers were combined, washed with 2N
aqueous sodium hydroxide solution and brine, and dried over
anhydrous sodium sulfate. The solvent was removed, and the residue
was purified by silica gel column chromatography (eluted with
hexane:ethyl acetate=20:1) to obtain 19.7 g (82.8 mmol, Yield:
82.8%) of tert-butyl-2-[(2-methoxyethoxy)methoxy]benzene.
(2) 1-Bromo-3-tert-butyl-2-[(2-methoxyethoxy)methoxy]-benzene
In dry ether (120 mL) was dissolved 10.0 g (42.0 mmol) of
tert-butyl-2-[(2-methoxyethoxy)methoxy]benzene obtained in (1),
42.1 mL (64.4 mmol) of n-butyl lithium-hexane solution (1.53M) was
added dropwise to the solution in an ice bath, and the mixture was
stirred in an ice bath for 3 hours. To the mixture was added
dropwise a dry ether (20 mL) solution containing 14.8 g (126 mmol)
of 90% cyanogen bromide. The reaction mixture was stirred in an ice
bath for 3 hours, poured into ice-cold water (300 mL), and
extracted with ether. The organic layers were combined, washed with
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (eluted with hexane:ethyl acetate=20:1) to obtain
8.48 g (26.8 mmol, Yield: 63.8%) of
1-bromo-3-tert-butyl-2-[(2-methoxyethoxy)methoxy]benzene.
(3) 2-Bromo-6-tert-butylphenol
In dichloromethane (30 mL) was dissolved 8.38 g (26.4 mmol) of
1-bromo-3-tert-butyl-2-[(2-methoxyethoxy)methoxy]-benzene obtained
in (2), a dichloromethane (20 mL) solution containing 9.03 g (79.2
mmol) of trifluoroacetic acid was added to the solution, and the
mixture was stirred at room temperature overnight. The reaction
mixture was poured into ice-cold 1 mol/L of hydrochloric acid, and
extracted with ethyl acetate. The organic layers were combined,
washed with brine, and dried over anhydrous sodium sulfate. The
solvent was removed, and the residue was purified by silica gel
column chromatography (eluted with hexane) to obtain 5.68 g (24.8
mmol, Yield: 93.9%) of 2-bromo-6-tert-butylphenol.
(4) 3-(2-Bromo-6-tert-butylphenoxy)-6-fluoropyridazine (Step
A-1)
In 1,4-dioxane (40 mL) was dissolved 4.84 g (21.1 mmol) of
2-bromo-6-tert-butylphenol obtained in (3), 3.55 g (31.7 mmol) of
potassium tert-butoxide and 1,4-dioxane (40 mL) were added to the
solution, and the mixture was stirred at room temperature for 15
minutes. To the mixture was added 2.45 g (21.1 mmol) of
3,6-difluoropyridazine and the resulting mixture was refluxed for
24 hours with stirring. The reaction mixture was allowed to stand
for cooling, poured into ice-cold water, and extracted with ethyl
acetate. The organic layers were combined, washed with brine, and
dried over anhydrous sodium sulfate. The solvent was removed, and
the obtained residue was purified by silica gel column
chromatography (hexane: ethyl acetate, gradient) to obtain 1.70 g
(5.23 mmol, Yield: 24.8%) of
3-(2-bromo-6-tert-butylphenoxy)-6-fluoropyridazine.
(5) 6-(2-Bromo-6-tert-butylphenoxy)-3-pyridazinol
1.04 g (10.6 mmol) of potassium acetate was added to a mixture of
acetic acid (9 mL) and 1.70 g (5.23 mmol) of
3-(2-bromo-6-tert-butylphenoxy)-6-fluoropyridazine obtained in (4),
and the resulting mixture was stirred at 130-140.degree. C. for 3
hours. The reaction mixture was allowed to stand for cooling,
poured into ice-cold water, and extracted with ethyl acetate. The
organic layers were combined, washed with brine, and dried over
anhydrous sodium sulfate. The solvent was removed, and the obtained
residue was washed with benzene to obtain 1.54 g (4.77 mmol, Yield:
91.2%, m.p. 255-257.degree. C.) of
6-(2-bromo-6-tert-butylphenoxy)-3-pyridazinol.
(6) 3-(2-Bromo-6-tert-butylphenoxy)-6-chloropyridazine
1.54 g (4.77 mmol) of 6-(2-bromo-6-tert-butylphenoxy)-3-pyridazinol
obtained in (5) was mixed with 15 mL (162 mmol) of phosphorus
oxychloride, and the mixture was refluxed for 70 minutes.
Phosphorus oxychloride was removed from the reaction mixture by
distillation, the reaction mixture was poured into ice-cold water,
and extracted with ethyl acetate. The organic layers were combined,
washed with brine, and dried over anhydrous sodium sulfate. The
solvent was removed to obtain 1.55 g (4.53 mmol, Yield: 95.0%) of
3-(2-bromo-6-tert-butylphenoxy)-6-chloropyridazine.
(7) Mixture of 3-(2-bromo-6-tert-butylphenoxy)-6-chloropyridazine
1-oxide and 6-(2-bromo-6-tert-butylphenoxy)-3-chloropyridazine
1-oxide (Step C-1)
In dry dichloromethane (20 mL) was dissolved 1.42 g (4.15 mmol) of
3-(2-bromo-6-tert-butylphenoxy)-6-chloropyridazine obtained in (6),
a dry dichloromethane (10 mL) solution containing 1.08 g (4.99
mmol) of 80% m-chloroperbenzoic acid was added to the solution, and
the mixture was refluxed for 20 hours. To the reaction mixture was
additionally added 0.275 g (1.27 mmol) of 80% m-chloroperbenzoic
acid, and after refluxing for 3 hours and 30 minutes, the reaction
mixture was poured into 1 mol/L aqueous sodium hydroxide solution,
and extracted with ethyl acetate. The organic layers were combined,
washed with brine, and dried over anhydrous sodium sulfate. The
solvent was removed, and the obtained residue was purified by
silica gel column chromatography (hexane: ethyl acetate=10:1) to
obtain 0.704 g (1.97 mmol, Yield: 47.5%) of a mixture of
3-(2-bromo-6-tert-butylphenoxy)-6-chloropyridazine 1-oxide and
6-(2-bromo-6-tert-butylphenoxy)-3-chloropyridazine 1-oxide.
(8) 3-(2-Bromo-6-tert-butylphenoxy)-4,6-dichloropyridazine and
6-(2-bromo-6-tert-butylphenoxy)-3,4-dichloropyridazine (Step
C-2)
0.704 g (1.97 mmol) of a mixture of
3-(2-bromo-6-tert-butylphenoxy)-6-chloropyridazine 1-oxide and
6-(2-bromo-6-tert-butylphenoxy)-3-chloropyridazine 1-oxide obtained
in (7) was mixed with 5 mL (54 mmol) of phosphorus oxychloride, and
the resulting mixture was refluxed for 2 hours. The reaction
mixture was allowed to stand for cooling, poured into ice-cold
water, and extracted with ethyl acetate. The organic layers were
combined, washed with brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the obtained residue was
purified by silica gel column chromatography (hexane:ethyl
acetate=20:1) to obtain 0.474 g (1.26 mmol, Yield: 64.0%) of
3-(2-bromo-6-tert-butylphenoxy)-4,6-dichloropyridazine and 0.119 g
(0.316 mmol, Yield: 16.0%) of
6-(2-bromo-6-tert-butylphenoxy)-3,4-dichloropyridazine.
(9) 3-(2-Bromo-6-tert-butylphenoxy)-6-chloro-4-methoxypyridazine
(Step C-3)
In methanol (10 mL) was dissolved 0.443 g (1.18 mmol) of
3-(2-bromo-6-tert-butylphenoxy)-4,6-dichloropyridazine obtained in
(8), and 0.545 g (2.83 mmol) of 28% sodium methoxide-methanol
solution and methanol (5 mL) were added to the solution, and the
resulting mixture was stirred at room temperature for 80 minutes.
To the reaction mixture was additionally added 0.10 g (0.52 mmol)
of 28% sodium methoxide-methanol solution, after stirring at room
temperature for 2 hours, 0.15 g (0.78 mmol) of 28% sodium
methoxide-methanol solution was further additionally added to the
mixture and the resulting mixture was stirred at room temperature
overnight. The reaction mixture was poured into ice-cold water, and
extracted with ethyl acetate. The organic layers were combined,
washed with brine, and dried over anhydrous sodium sulfate. The
solvent was removed to obtain 0.428 g (1.15 mmol, Yield: 97.5%) of
3-(2-bromo-6-tert-butylphenoxy)-6-chloro-4-methoxypyridazine:
(10) 3-(2-Bromo-6-tert-butylphenoxy)-6-chloro-4-pyridazinol
(Compound No. 761, Step C-4)
In dimethylsulfoxide (5 mL) was dissolved 0.395 g (1.06 mmol) of
3-(2-bromo-6-tert-butylphenoxy)-6-chloro-4-methoxypyridazine
obtained in (9), aqueous sodium hydroxide solution (prepared by
dissolving 50.8 mg of sodium hydroxide in 3 mL of water, 1.27 mmol)
was added to the solution, and the resulting mixture was stirred at
80.degree. C. for 3 hours. Aqueous sodium hydroxide solution
(prepared by dissolving 42 mg of sodium hydroxide in 3 mL of water,
1.1 mmol) and dimethylsulfoxide (10 mL) were additionally added
thereto, and the mixture was further stirred at 80.degree. C. for 5
hours. After cooling by allowing to stand, the reaction mixture was
poured into ice-cold water, and made acidic by hydrochloric acid.
The precipitated solid was collected by filtration, washed
successively with water, hexane and isopropyl ether, and air-dried.
0.309 g (0.863 mmol, Yield: 81.4%) of
3-(2-bromo-6-tert-butylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 761) was obtained.
.sup.1H-NMR (270 MHz, CDCl.sub.3) .delta. ppm: 9.55 (1H, brs), 7.47
(1H, dd, J=8.1, 1.7 Hz), 7.41 (1H, dd, J=8.1, 1.7 Hz), 7.08 (1H, t,
J=8.1 Hz), 6.58 (1H, brs), 1.34 (9H, s). Melting point (.degree.
C.): 240-247.
EXAMPLE 21
6-Chloro-3-(2,6-dimethylphenoxy)-4-pyridazinol (Compound No.
801)
(1) 6-Chloro-3-(2,6-dimethylphenoxy)pyridazine 1-oxide (Step
B-2)
268 mg (2.20 mmol) of 2,6-dimethylphenol, 1,4-dioxane (3 mL) and
dimethylsulfoxide (3 mL) were mixed, 270 mg (2.41 mmol) of
potassium tert-butoxide was added to the mixture in an ice bath,
and the resulting mixture was stirred for 10 minutes. To the
mixture was added 370 mg (2.24 mmol) of 3,6-dichloropyridazine
1-oxide, and the resulting mixture was stirred at room temperature
for 10 hours and allowed to stand for 2 days. The reaction mixture
was poured into ice-cold water, and extracted with ethyl acetate.
The organic layers were combined, washed successively with water
and brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (hexane: ethyl acetate, gradient) to obtain 350 mg
(1.39 mmol, Yield: 63.1%) of
6-chloro-3-(2,6-dimethylphenoxy)pyridazine 1-oxide.
(2) 4,6-Dichloro-3-(2,6-dimethylphenoxy)pyridazine (Step B-3)
330 mg (1.31 mmol) of 6-chloro-3-(2,6-dimethylphenoxy)pyridazine
1-oxide obtained in (1) was mixed with dichloromethane (0.6 mL) and
phosphorus oxychloride 0.60 mL (6.5 mmol), and the mixture was
stirred for 1 hour and allowed to stand for further 5 days. The
reaction mixture was poured into ice-cold water, and extracted with
ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the residue was purified by
silica gel column chromatography (hexane: ethyl acetate, gradient)
to obtain 322 mg (1.20 mmol, Yield: 91.6%) of
4,6-dichloro-3-(2,6-dimethylphenoxy)-pyridazine.
(3) 6-Chloro-3-(2,6-dimethylphenoxy)-4-pyridazinol (Compound No.
801, Step B-4)
In dimethylsulfoxide (8 mL) was dissolved 300 mg (1.12 mmol) of
4,6-dichloro-3-(2,6-dimethylphenoxy)-pyridazine obtained in (2),
0.80 mL (2.0 mmol) of 10% (W/V) aqueous sodium hydroxide solution
was added to the solution, and the resulting mixture was stirred at
room temperature overnight. To the mixture was further added. 0.80
mL (2.0 mmol) of 10% (W/V) aqueous sodium hydroxide solution, and
after disappearance of the starting materials, the reaction mixture
was poured into ice-cold water. The mixture was made acidic with
hydrochloric acid, and then, extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (hexane:ethyl acetate, gradient) and purified by
preparative thin-layer chromatography (available from Merck Co.,
1.05744, developed by dichloromethane: methanol=9:1) to obtain 128
mg (0.510 mmol, Yield: 45.5%) of
6-chloro-3-(2,6-dimethylphenoxy)-4-pyridazinol (Compound No.
801).
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.18-7.05 (3H, m),
6.83 (1H, s), 2.05 (6H, s). Melting point (.degree. C.):
214-215.
EXAMPLE 22
3-(2-tert-Butyl-6-methylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 805)
(1) 3-(2-tert-Butyl-6-methylphenoxy)-6-chloropyridazine (Step
A-1)
17.5 g (107 mmol) of 2-tert-butyl-6-methylphenol, 11.9 g (106 mmol)
of potassium tert-butoxide and 1,4-dioxane (250 mL) were mixed, and
the mixture was stirred at room temperature for 30 minutes. To the
mixture was added 15.0 g (101 mmol) of 2,6-dichloropyridazine and
the resulting mixture was stirred at 100.degree. C. for 3 hours and
15 minutes. The reaction mixture was poured into ice water, and
extracted with ethyl acetate. The organic layer was washed
successively with water and brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the residue was crystallized
form isopropyl ether to obtain 15.3 g (55.2 mmol, Yield: 54.6%) of
3-(2-tert-butyl-6-methylphenoxy)-6-chloropyridazine.
(2) 3-(2-tert-Butyl-6-methylphenoxy)-6-chloropyridazine 1-oxide
(Step C-1)
8.00 g (28.9 mmol) of
3-(2-tert-butyl-6-methylphenoxy)-6-chloropyridazine obtained in (1)
was mixed with dry dichloromethane (200 mL) and 8.50 g (34.4 mmol)
of 70% m-chloroperbenzoic acid, and the mixture was stirred at room
temperature for 4 days. The reaction mixture was poured into an
ice-coled saturated aqueous sodium sulfite solution, and extracted
with dichloromethane. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the residue was crystallized
from a mixed solvent of ether-hexane or purified by silica gel
column chromatography to obtain 7.04 g (24.0 mmol, Yield: 83.0%) of
3-(2-tert-butyl-6-methylphenoxy)-6-chloropyridazine 1-oxide.
(3) 3-(2-tert-Butyl-6-methylphenoxy)-4,6-dichloropyridazine (Step
C-2)
1.00 g (3.41 mmol) of
3-(2-tert-butyl-6-methylphenoxy)-6-chloropyridazine 1-oxide
obtained in (2) was mixed with chloroform (10 mL) and 0.48 mL (5.2
mmol) of phosphorus oxychloride, and the mixture was stirred under
reflux for 24 hours and at room temperature for 2 days. The
reaction mixture was poured into ice-cold water, and extracted with
dichloromethane. The organic layers were combined, washed
successively with a saturated aqueous sodium hydrogen carbonate
solution, water and brine, and dried over anhydrous sodium sulfate.
The solvent was removed and the residue was crystallized from a
mixed solvent of ether-hexane to obtain 0.767 g (2.47 mmol, Yield:
72.4%) of
3-(2-tert-butyl-6-methylphenoxy)-4,6-dichloropyridazine.
(4) 3-(2-tert-Butyl-6-methylphenoxy)-6-chloro-4-pyridazinol
(Compound No. 805, Step C-3)
354 mg (1.14 mmol) of
3-(2-tert-butyl-6-methylphenoxy)-4,6-dichloropyridazine obtained in
(3) was mixed with dimethylsulfoxide (10 mL) and 1.6 mL (1.6 mmol)
of 1 mol/L aqueous sodium hydroxide solution, and the mixture was
stirred at room temperature for 2 hours and 30 minutes. The
reaction mixture was poured into ice-cold water, and washed with
ether. The aqueous layer was made acidic with hydrochloric acid,
and extracted with ethyl acetate. The organic layer was washed with
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was crystallized from a mixed solvent of
ether-hexane to obtain 172 mg (0.587 mmol, Yield: 51.5%) of
3-(2-tert-butyl-6-methylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 805).
.sup.1H-NMR (90 MHz, CDCl.sub.3) .delta. ppm: 7.35-6.80 (3H, m),
6.50 (1H, s), 1.80 (3H, s), 1.18 (9H, s). Melting point (.degree.
C.): 135-136.
EXAMPLE 23
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (Compound
No. 806)
(1) 6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)pyridazine 1-oxide
and 3-chloro-6-(2-cyclopropyl-6-methylphenoxy)pyridazine 1-oxide
(Step B-2)
221 mg (1.49 mmol) of 2-cyclopropyl-6-methylphenol was mixed with
1,4-dioxane (2 mL) and dimethylsulfoxide (2 mL), 184 mg (1.64 mmol)
of potassium tert-butoxide was added to the mixture in an ice bath,
and the resulting mixture was stirred for 10 minutes. To the
mixture was added 258 mg (1.56 mmol) of 3,6-dichloropyridazine
1-oxide, and the resulting mixture was stirred at room temperature
for 10 hours, and then, allowed to stand for 3 days. The reaction
mixture was poured into ice-cold water, and extracted with ethyl
acetate. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous sodium sulfate. The
solvent was removed, and the residue was purified by silica gel
column chromatography (hexane:ethyl acetate, gradient) to obtain
222 mg (0.801 mmol, Yield: 53.8%) of a mixture of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-cyclopropyl-6-methylphenoxy)pyridazine 1-oxide.
(2) 4,6-Dichloro-3-(2-cyclopropyl-6-methylphenoxy)-pyridazine (Step
B-3)
In chloroform (1 mL) was dissolved 210 mg (0.758 mmol) of a mixture
of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-cyclopropyl-6-methylphenoxy)pyridazine 1-oxide
obtained in (1), 0.106 mL (1.14 mmol) of phosphorus oxychloride was
added to the mixture, and after removing almost all the chloroform
with a nitrogen-stream, the mixture was stirred at room temperature
for 2 days. Further, chloroform (2 mL) and 0.150 mL (1.62 mmol) of
phosphorus oxychloride were added to the mixture, and after
removing almost all the chloroform with a nitrogen stream, the
mixture was stirred for 3 hours. The reaction mixture was poured
into ice-cold water, and extracted with ethyl acetate. The organic
layers were combined, washed successively with water, brine, and
dried over anhydrous sodium sulfate. The solvent was removed, and
the residue was purified by silica gel column chromatography
(hexane:ethyl acetate, gradient) to obtain 167 mg (0.566 mmol,
Yield: 74.7%) of
4,6-dichloro-3-(2-cyclopropyl-6-methylphenoxy)pyridazine.
(3) 6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol
(Compound No. 806, Step B-4)
In dimethylsulfoxide (3 mL) was dissolved 150 mg (0.508 mmol) of
4,6-dichloro-3-(2-cyclopropyl-6-methylphenoxy)pyridazine obtained
in (2), 0.37 mL (0.925 mmol) of 10% (W/V) aqueous sodium hydroxide
solution was added to the solution, and the mixture was stirred at
room temperature for 4 days. The reaction mixture was poured into
an ice-coled 5% aqueous sodium hydroxide solution, and extracted
with ether. The aqueous layer was made acidic with hydrochloric
acid, and extracted with ether. The organic layer was dried and
concentrated. The residue was purified by preparative thin-layer
chromatography (available from Merck Co., 1.05744, developed by
dichloromethane: methanol=20:1) to obtain 114 mg (0.412 mmol,
Yield: 81.1%) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (Compound
No. 806).
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.13-7.03 (2H, m),
6.84-6.79 (2H, m), 2.06 (3H, s), 1.83-1.68 (1H, m), 0.82-0.72 (2H,
m), 0.64-0.51 (2H, m). Melting point (.degree. C.): 201-202.
EXAMPLE 24
6-Chloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]-4-pyridazinol
(Compound No. 827)
(1) 1-(2,2-Dichlorocyclopropyl)-2-methoxy-3-methylbenzene
In chloroform (12 mL) was dissolved 304 mg (2.05 mmol) of
2-methoxy-1-methyl-3-vinylbenzene, 5 mL (63 mmol) of 50% aqueous
sodium hydroxide solution was added dropwise to the solution, then,
59.9 mg (0.263 mmol) of benzyl-(triethyl)ammonium chloride was
added to the mixture, and the resulting mixture was stirred at room
temperature overnight. The reaction mixture was poured into water,
and extracted with chloroform. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was distilled off and the obtained residue was
purified by preparative thin-layer chromatography (available from
MERCK CO., 1.05744, 3 plates were used, developed by hexane:ethyl
acetate=4:1) to obtain 390 mg (1.69 mmol, Yield: 82.4%) of
1-(2,2-dichlorocyclopropyl)-2-methoxy-3-methylbenzene.
(2) 2-(2,2-Dichlorocyclopropyl)-6-methylphenol
In dichloromethane (5 mL) was dissolved 102 mg (0.442 mmol) of
1-(2,2-dichlorocyclopropyl)-2-methoxy-3-methylbenzene obtained in
(1), the solution was cooled in an ice bath, and 0.045 mL (0.47
mmol) of boron tribromide was added dropwise to the solution with
stirring. The reaction mixture was stirred in an ice bath for 2
hours, and then, poured into water and extracted with
dichloromethane. The organic layer was successively washed with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 2 plates were used, developed by hexane:ethyl acetate=2:1)
to obtain 76.9 mg (0.354 mmol, Yield: 80.1%) of
2-(2,2-dichlorocyclopropyl)-6-methylphenol.
(3)
6-Chloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]pyridazine
1-oxide (Step B-2)
198 mg (0.912 mmol) of 2-(2,2-dichlorocyclopropyl)-6-methylphenol
obtained in (2) was mixed with 1,4-dioxane (3 mL) and
dimethylsulfoxide (3 mL), 113 mg (1.01 mmol) of potassium
tert-butoxide was added to the mixture in an ice bath, and the
resulting mixture was stirred for 10 minutes.
To the mixture was added 151 mg (0.915 mmol) of
3,6-dichloropyridazine 1-oxide, and the resulting mixture was
stirred at room temperature overnight. The reaction mixture was
poured into ice-cold water, and extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 3
plates were used, developed by hexane:ethyl acetate=2:1 three
times) to obtain 257 mg of a crude product of
6-chloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]pyridazine
1-oxide.
(4)
4,6-Dichloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]pyridazine
(Step B-3)
257 mg of a crude product of
6-chloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]pyridazine
1-oxide obtained in (3) was mixed with phosphorus oxychloride (3
mL), and the mixture was stirred at room temperature overnight. To
the reaction mixture were added water and dichloromethane, and the
resulting mixture was stirred for 30 minutes. This mixture was
separated, the organic layer was successively washed with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 3
plates were used, developed by hexane:ethyl acetate=2:1) to obtain
209 mg (0.574 mmol, Yield from
2-(2,2-dichlorocyclopropyl)-6-methylphenol with 2 Steps: 62.9%) of
4,6-dichloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]pyridazine.
(5)
6-Chloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]-4-pyridazinol
(Compound No. 827, Step B-4)
209 mg (0.574 mmol)-of
4,6-dichloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]pyridazine
obtained in (4) was mixed with 1,4-dioxane (3 mL) and
dimethylsulfoxide (3 mL), 1.43 mL (2.86 mmol) of 2 mol/L aqueous
sodium hydroxide solution was added to the mixture, and the
resulting mixture was stirred at room temperature over-night. The
reaction mixture was poured into water, and made acidic with
diluted hydrochloric acid. This mixture was extracted with
dichloromethane. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the residue
was purified by preparative thin-layer chromatography (available
from MERCK CO., 1.05744, 3 plates were used, developed by ethyl
acetate) to obtain 120 mg (0.349 mmol, Yield: 60.8%) of
6-chloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]-4-pyridazinol
(Compound No. 827).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.25 (1H, br.d,
J=6.3 Hz), 7.16 (1H, t, J=7.7 Hz), 6.98 (1H, d, J=7.7 Hz), 6.72
(1H, s), 2.85 (1H, dd, J=10.6, 8.8 Hz), 2.22 (3H, s), 2.05-1.86
(2H, m). Melting point (.degree. C.): 213-215.
EXAMPLE 25
6-Chloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]-4-pyridazinol
(Compound No. 1109)
(1) 6,7-Dihydro-1-benzofuran-4(5H)-one
In methanol (40 mL) was dissolved 11.2 g (0.100 mol) of
1,3-cyclohexanedione, an aqueous solution (8 mL) containing 6.60 g
(0.100 mol) of 85% potassium hydroxide was added dropwise to the
solution, and the resulting mixture was stirred at room temperature
for 30 minutes. This mixture was cooled in an ice bath, 21.6 g
(0.110 mol) of 40% chloroacetaldehyde aqueous solution was added to
the mixture with stirring and the resulting mixture was stirred at
room temperature overnight. To the reaction mixture was added
dropwise 2 mol/L hydrochloric acid aqueous solution, and the
resulting mixture was stirred at room temperature for 30 minutes
and extracted with ether. The organic layer was successively washed
with water and brine, and dried over anhydrous magnesium sulfate.
The solvent was removed, and the obtained residue was purified by
silica gel column chromatography (Wako gel C-100, hexane-ethyl
acetate, gradient) to obtain 8.63 g (0.0635 mol, Yield: 63.5%) of
6,7-dihydro-1-benzofuran-4(5H)-one.
(2) Methyl 4-oxo-4,5,6,7-tetrahydro-1-benzofuran-5-carboxylate
In dry tetrahydrofuran (10 mL) was dissolved 3.00 g (22.1 mmol) of
6,7-dihydro-1-benzofuran-4(5H)-one obtained in (1), and 48.5 mL
(48.5 mmol) of lithium bis(trimethylsilyl)amide (1.0 M
tetrahydrofuran solution) was added dropwise to the solution under
nitrogen atmosphere at -78.degree. C. After stirring at -78.degree.
C. for 30 minutes, 1.87 mL (24.1 mmol) of methyl chlorocarbonate
was added dropwise to the mixture, and the reaction mixture was
warmed to room temperature and stirred for 10 minutes. The reaction
mixture was poured into water, and extracted with ethyl acetate.
The organic layer was successively washed with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was removed,
and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate, gradient) to
obtain 3.93 g (20.3 mmol, Yield: 91.9%) of methyl
4-oxo-4,5,6,7-tetrahydro-1-benzofuran-5-carboxylate.
(3) Methyl 4-hydroxy-1-benzofuran-5-carboxylate
In 1,4-dioxane (100 mL) was dissolved 3.93 g (20.3 mmol) of methyl
4-oxo-4,5,6,7-tetrahydro-1-benzofuran-5-carboxylate obtained in
(2), 5.51 g (24.3 mmol) of
2,3-dichloro-5,6-dicyano-1,4-benzoquinone was added to the
solution, and the resulting mixture was stirred at 120.degree. C.
for 3 hours. The reaction mixture was allowed to stand for cooling,
insoluble materials were filtered off through Celite, and the
filtrate was concentrated. The residue was purified by silica gel
column chromatography (Wako gel C-100, hexane-ethyl acetate,
gradient) to obtain 2.04 g (10.6 mmol, Yield: 52.2%) of methyl
4-hydroxy-1-benzofuran-5-carboxylate.
(4) Methyl 4-methoxy-1-benzofuran-5-carboxylate
To an acetonitrile (60 mL) solution containing 2.04 g (10.6 mmol)
of methyl 4-hydroxy-1-benzofuran-5-carboxylate obtained in (3) were
added 2.53 g (18.3 mmol) of potassium carbonate, and then, 2.85 mL
(45.8 mmol) of methyl iodide, and the resulting mixture was
refluxed for 3 hours. After allowing to stand at room temperature
overnight, the reaction mixture was poured into water, and
extracted with ethyl acetate. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was removed, and the obtained residue was
purified by silica gel column chromatography (Wako gel C-100,
hexane-ethyl acetate, gradient) to obtain 2.01 g (9.76 mmol, Yield:
92.1%) of methyl 4-methoxy-1-benzofuran-5-carboxylate.
(5) (4-Methoxy-1-benzofuran-5-yl)methanol
To a dry tetrahydrofuran (20 mL) solution containing 1.01 g (4.90
mmol) of methyl 4-methoxy-1-benzofuran-5-carboxylate obtained in
(4), 0.479 g (12.6 mmol) of lithium aluminum hydride was added
little by little to the mixture in an ice bath with stirring. The
reaction mixture was stirred in an ice bath for 2 hours, and ethyl
acetate was added little by little to the mixture. Subsequently,
water (0.5 mL), 3N sodium hydroxide (0.5 mL), and water (1.5 mL)
were successively added to the mixture and the resulting mixture
was stirred for 30 minutes. This mixture was filtered through
Celite, and the filtrate was concentrated to obtain 0.89 g of a
crude product of (4-methoxy-1-benzofuran-5-yl)methanol.
(6) 4-Methoxy-5-methyl-1-benzofuran
In dichloromethane (10 mL) was dissolved 0.65 g of a crude product
of (4-methoxy-1-benzofuran-5-yl)methanol obtained in (5), 0.56 mL
(4.03 mmol) of triethylamine, and then, 0.31 mL (3.99 mmol) of
methanesulfonyl chloride were added dropwise to the solution in an
ice bath with stirring, and the resulting mixture was stirred in an
ice bath for 1 hour. The reaction mixture was poured into water,
and extracted with ethyl acetate. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, dry dimethylsulfoxide
(20 mL) was added to the obtained residue, and 0.276 g (7.30 mmol)
of sodium borohydride was added little by little. This mixture was
stirred at room temperature for 1 hour, then poured into water, and
extracted with ethyl acetate. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was distilled off and the obtained residue was
purified by preparative thin-layer chromatography (available from
MERCK CO., 1.05717, 3 plates were used, developed by hexane:ethyl
acetate=9:1) to obtain 0.284 g (1.75 mmol, Yield from methyl
4-methoxy-1-benzofuran-5-carboxylate: 48.9%) of
4-methoxy-5-methyl-1-benzofuran.
(7) 5-Methyl-1-benzofuran-4-ol
In dry N,N-dimethylformamide (11 mL) was suspended 268 mg (6.71
mmol) of 60% sodium hydride, 0.51 mL (6.9 mmol) of ethanethiol was
added dropwise to the suspension under nitrogen atmosphere, and the
resulting mixture was stirred at room temperature for 10 minutes.
To the mixture was added a N,N-dimethylformamide (7 mL) solution
containing 362 mg (2.23 mmol) of 4-methoxy-5-methyl-1-benzofuran
obtained in (6), and the resulting mixture was refluxed for 1 hour
and 30 minutes. The reaction mixture was allowed to stand for
cooling, and 1 mol/L potassium hydroxide aqueous solution and
diethyl ether were added thereto. The aqueous layer was washed with
diethyl ether, and a pH thereof was adjusted by adding diluted
hydrochloric acid thereto to a pH 2. The mixture was extracted with
diethyl ether, the obtained organic layer was successively washed
with water and brine, and dried over anhydrous magnesium sulfate.
The solvent was distilled off and the obtained residue was purified
by preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 3 plates were used, developed by hexane:ethyl acetate=2:1)
to obtain 276 mg (1.86 mmol, Yield: 83.4%) of
5-methyl-1-benzofuran-4-ol.
(8) 6-Chloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]pyridazine 1-oxide
(Step B-2)
121 mg (0.818 mmol) of 5-methyl-1-benzofuran-4-ol obtained in (7)
was mixed with 1,4-dioxane (3 mL) and dimethylsulfoxide (3 mL), 101
mg (0.902 mmol) of potassium tert-butoxide was added to the mixture
in an ice bath, and the resulting mixture was stirred for 10
minutes. To the mixture was added 134 mg (0.812 mmol) of
3,6-dichloropyridazine 1-oxide, and the resulting mixture was
stirred at room temperature overnight. The reaction mixture was
poured into ice-cold water, and extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 3
plates were used, developed by hexane:ethyl acetate=2:1 three
times) to obtain 199 mg of a crude product of
6-chloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]pyridazine 1-oxide.
(9) 4,6-Dichloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]-pyridazine
(Step B-3)
199 mg of a crude product of
6-chloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]pyridazine 1-oxide
obtained in (8) and 3 mL of phosphorus oxychloride were mixed, and
the mixture was stirred at room temperature overnight. To the
reaction mixture were added water and dichloromethane, and the
resulting mixture was stirred for 30 minutes. The mixture was
separated, the organic layer was successively washed with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 3
plates were used, developed by hexane:ethyl acetate=2:1 three
times, subsequently available from MERCK CO., 1.05717, 2 plates
were used, developed by hexane:ethyl acetate=2:1 three times) to
obtain 120 mg (0.407 mmol, Yield from
4-hydroxy-5-methyl-1-benzofuran with 2 Steps: 49.8%) of
4,6-dichloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]pyridazine.
(10) 6-Chloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]-4-pyridazinol
(Compound No. 1109, Step B-4)
120 mg (0.407 mmol) of
4,6-dichloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]pyridazine obtained
in (9) was mixed with 1,4-dioxane (3 mL) and dimethylsulfoxide (3
mL), 1.01 mL (2.02 mmol) of 2 mol/L aqueous sodium hydroxide
solution was added to the mixture, and the resulting mixture was
stirred at room temperature overnight. The reaction mixture was
poured into water, and made acidic with diluted hydrochloric acid.
This mixture was extracted with dichloromethane. The organic layers
were combined, washed successively with water and brine, and dried
over anhydrous magnesium sulfate. The solvent was distilled off and
the residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 2 plates were used, developed
by ethyl acetate) to obtain 70.0 mg (0.253 mmol, Yield: 62.2%) of
6-chloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]-4-pyridazinol
(Compound No. 1109).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.65 (1H, d, J=2.2
Hz), 7.32 (1H, d, J=8.8 Hz), 7.18 (1H, d, J=8.8 Hz), 6.73 (1H, s),
6.60 (1H, dd, J=2.2, 0.7 Hz), 2.23 (3H, s). Melting point (.degree.
C.): 222-225.
EXAMPLE 26
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl
trifluoromethanesulfonate (Compound No. 2081, Step I-1)
In methylene chloride (2 mL) was dissolved 50.3 mg (0.191 mmol) of
6-chloro-3-(2-cyclopropylphenoxy)-4-pyridazinol (Compound No. 139)
obtained in Example 6, 0.027 mL (0.19 mmol) of triethylamine was
added dropwise to the solution, then, 0.031 mL (0.19 mmol) of
trifluoromethanesulfonic acid anhydride was added dropwise to the
same, and the resulting mixture was stirred at room temperature for
30 minutes. The reaction mixture was purified as such by
preparative thin-layer chromatography (available from MERCK Co.,
1.05744, 2 plates were used, developed by ethyl acetate:hexane=2:1)
to obtain 64.7 mg (0.164 mmol, Yield: 85.8%) of
6-chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl
trifluoromethanesulfonate (Compound No. 2081).
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.51 (1H, s),
7.26-7.19 (2H, m), 7.14-7.05 (2H, m), 1.89-1.81 (1H, m), 0.85-0.62
(4H, m). Melting point (.degree. C.): 54-61.
EXAMPLE 27
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl 4-methylbenzene
sulfonate (Compound No. 2225, Step I-1)
In acetonitrile (3 mL) was dissolved 53.4 mg (0.203 mmol) of
6-chloro-3-(2-cyclopropylphenoxy)-4-pyridazinol (Compound No. 139)
obtained in Example 6, 23.1 mg (0.206 mmol) of
1,4-diazabicyclo[2,2,2]octane was added to the solution, then, 39.2
mg (0.205 mmol) of 4-methylbenzene sulfonyl chloride was added to
the same, and the resulting mixture was stirred at room temperature
for 1 hour and 30 minutes. The reaction mixture was poured into
water, and extracted with ethyl acetate. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, ethyl acetate:hexane=2:1) to
obtain 68.8 mg (0.165 mmol, Yield: 81.3%) of
6-chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl 4-methylbenzene
sulfonate (Compound No. 2225).
H.sup.1-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.87 (2H, d, J=8.1
Hz), 7.58 (1H, s), 7.36 (2H, d, J=8.1 Hz), 7.26-7.11 (2H, m),
6.97-6.93 (1H, m), 6.74-6.70 (1H, m), 2.45 (3H, s), 1.67-1.59 (1H,
m), 0.71-0.56 (4H, m). Appearance: oily product.
EXAMPLE 28
2-[(6-Chloro-4-{[(4-methylphenyl)sulfonyl]oxy}-3-pyridazinyl)oxy]phenyl
4-methylbenzene sulfonate (Compound No. 2233, Step I-1)
0.60 g (2.5 mmol) of 6-chloro-3-(2-hydroxyphenoxy)-4-pyridazinol
(Compound No. 384) obtained in Example 10, 1.06 g (5.5 mmol) of
4-methylbenzene sulfonyl chloride, 0.56 g (5.0 mmol) of
1,4-diazabicyclo[2,2,2]octane and acetonitrile (30 mL) were mixed,
and the mixture was stirred under reflux for 3 hours, and at room
temperature for 4 days. Acetonitrile was removed by distillation,
water was added to the residue, and the mixture was extracted with
ethyl acetate. The organic layers were combined, washed with water,
and dried over anhydrous sodium sulfate. The solvent was removed,
and the residue was washed with a mixed solvent of hexane-ethyl
acetate (3:1) to obtain 1.0 g (1.8 mmol, Yield: 72%) of
2-[(6-chloro-4-{[(4-methylphenyl)sulfonyl]oxy}-3-pyridazinyl)oxy]phenyl
4-methylbenzene sulfonate (Compound No. 2233).
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.98-6.65 (13H, m),
2.40 (3H, s), 2.36 (3H, s). Melting point (.degree. C.):
125.5-126.5.
EXAMPLE 29
6-Chloro-5-methyl-3-(2-methylphenoxy)-4-pyridazinol (Compound No.
2372)
(1) 3-Chloro-4-methyl-2,5-furandione and
3-chloro-4-(chloromethyl)-2,5-furandione
224 g (2.00 mol) of 3-methyl-2,5-furandione and 11.2 g (0.415 mol)
of iron chloride (III) hexahydrate were mixed, and the mixture was
heated to 140.degree. C., and 346 g (4.88 mol) of a chlorine gas
was passed through the mixture with stirring over 7 hours and 30
minutes. Thereafter, the mixture was heated at 175.degree. C. for 3
hours and 30 minutes. The reaction mixture was evaporated under
reduced pressure (5 mmHg) to collect fractions of 80.degree. C. to
85.degree. C. Thus, 223.5 g of a crude product (containing
3-chloro-4-methyl-2,5-furandione and
3-chloro-4-(chloromethyl)-2,5-furandione) was obtained.
(2) 4-Chloro-5-methyl-1,2-dihydro-3,6-pyridazinedione and
4-chloro-5-(chloromethyl)-1,2-dihydro-3,6-pyridazinedione
147 g of a material (containing 3-chloro-4-methyl-2,5-furandione
and 3-chloro-4-(chloromethyl)-2,5-furandione) obtained in (1) was
mixed with 400 mL of water, and the mixture was refluxed to make a
solution. To the solution heated at reflux was added dropwise an
aqueous solution containing 116 g (1.10 mol) of hydrazine
dihydrochloride (the hydrazine dihydrochloride was dissolved in 400
mL of water) over 40 minutes. Thereafter, the mixture was refluxed
for 1 hour and 30 minutes, and then allowed to stand for cooling.
Precipitated crystals were collected by filtration, washed with hot
water, and then, with ethyl acetate, to obtain 81.8 g of
4-chloro-5-methyl-1,2-dihydro-3,6-pyridazinedione (m.p.
305-310.degree. C.). On the other hand, the filtrate was extracted
with ethyl acetate, the organic layers were combined, washed with
water, and dried over anhydrous sodium sulfate. The solvent was
removed, and a mixture containing 8.06 g of
4-chloro-5-(chloromethyl)-1,2-dihydro-3,6-pyridazinedione was
obtained as a residue.
(3) 3,4,6-Trichloro-5-methylpyridazine
24.1 g (0.150 mol) of
4-chloro-5-methyl-1,2-dihydro-3,6-pyridazinedione obtained in (2)
was mixed with 250 mL (2.76 mol) of phosphorus oxychloride, and the
mixture was refluxed for 1 hour and 40 minutes. Excess phosphorus
oxychloride was removed from the reaction mixture by distillation,
and the residue was mixed with ice water. Crystals were collected
by filtration, and extracted with ethyl acetate. The organic layer
was washed with water, and the solvent was removed. The obtained
residue was distilled under reduced pressure (0.7 mmHg) and
fractions at 105.degree. C. to 110.degree. C. were collected to
obtain 25.1 g (0.127 mol, Yield: 84.7%, m.p. 67.5-70.degree. C.) of
3,4,6-trichloro-5-methylpyridazine.
(4) 3,6-Dichloro-4-methoxy-5-methylpyridazine
7.90 g (40.1 mmol) of 3,4,6-trichloro-5-methylpyridazine obtained
in (3) was mixed with methanol (100 mL), a methanol solution (50
mL) containing 0.92 g (40 mmol) of sodium was added dropwise to the
mixture in an ice bath, thereafter in an ice bath, the mixture was
stirred for 1 hour, and then, for 15 minutes under reflux. In an
ice bath, 0.20 g (8.7 mmol) of sodium was additionally added to the
mixture, and the resulting mixture was further refluxed for 15
minutes. The reaction mixture was allowed to stand for cooling, and
methanol was distilled off. The residue was mixed with ice water
and extracted with ethyl acetate. The organic layers were combined,
washed with water, and the solvent was removed. The obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, eluted with hexane:ethyl acetate=5:1) to obtain 5.1 g of a
crude product. This product was distilled under reduced pressure
(0.07 mmHg) and fractions at 125.degree. C. were collected to
obtain 4.50 g (23.3 mmol, Yield: 58.1%) of
3,6-dichloro-4-methoxy-5-methylpyridazine.
(5) Mixture of
3-chloro-5-methoxy-4-methyl-6-(2-methylphenoxy)pyridazine and
3-chloro-4-methoxy-5-methyl-6-(2-methylphenoxy)pyridazine (Step
D-1)
To 30.8 g (285 mmol) of 2-methylphenol was gradually added 1.66 g
(38.0 mmol) of 55% sodium hydride with stirring. After stirring at
room temperature for 20 minutes, the mixture was heated to
90.degree. C. to disappear a solid of sodium hydride. This mixture
was cooled to 50.degree. C., 3.69 g (19.1 mmol) of
3,6-dichloro-4-methoxy-5-methylpyridazine obtained in (4) was added
thereto, and the resulting mixture was stirred at 110.degree. C.
for 3 hours and 30 minutes. The reaction mixture was allowed to
stand for cooling, water was added thereto, and then, the mixture
was extracted with ethyl acetate. The organic layer was washed with
20% aqueous sodium hydroxide solution, and the solvent was removed.
The obtained residue was purified by silica gel column
chromatography to obtain 1.38 g (5.21 mmol, Yield: 27.3%) of a
mixture of
3-chloro-5-methoxy-4-methyl-6-(2-methylphenoxy)pyridazine and
3-chloro-4-methoxy-5-methyl-6-(2-methylphenoxy)pyridazine.
(6) 6-Chloro-5-methyl-3-(2-methylphenoxy)-4-pyridazinol (Compound
No. 2372, Step D-2)
1.38 g (5.21 mmol) of a mixture of
3-chloro-5-methoxy-4-methyl-6-(2-methylphenoxy)pyridazine and
3-chloro-4-methoxy-5-methyl-6-(2-methylphenoxy)pyridazine obtained
in (5) was mixed with 1,4-dioxane (8 mL), an aqueous solution
(using 13 mL of water) containing 0.282 g (6.78 mmol) of 96% sodium
hydroxide was added to the mixture, and the resulting mixture was
stirred at 110.degree. C. for 4.5 hours. Water was poured into the
reaction mixture, and the mixture was extracted with ethyl acetate.
The aqueous layer was made acidic with hydrochloric acid, and
precipitated crystals were collected by filtration to obtain 0.249
g (0.992 mmol, Yield: 19.0%, m.p. 209-213.degree. C.) of
6-chloro-5-methyl-3-(2-methylphenoxy)-4-pyridazinol (Compound No.
2372).
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.50-6.95 (4H, m),
2.28 (3H, m), 2.11 (3H, m). Melting point (.degree. C.):
209-213.
Incidentally, crystals precipitated from the filtrate were
collected by filtration to obtain 0.187 g (0.745 mmol, Yield:
14.3%) of 3-chloro-5-methyl-6-(2-methylphenoxy)-4-pyridazinol. On
the other hand, the organic layer was dried over anhydrous sodium
sulfate, and the solvent was removed to recover 0.57 g (Recovery:
41%) of the starting material.
EXAMPLE 30
6-Chloro-5-(methoxymethyl)-3-(2-methylphenoxy)-4-pyridazinol
(Compound No. 2378)
(1) 3,4,6-Trichloro-5-(chloromethyl)pyridazine
7.8 g of a mixture containing
4-chloro-5-(chloromethyl)-1,2-dihydro-3,6-pyridazinedione obtained
in Example 29 was added 50 mL of phosphorus oxychloride, and the
mixture was refluxed for 1 hour. Excess phosphorus oxychloride was
distilled off from the reaction mixture, and the residue was mixed
with ice water. The mixture was extracted with ethyl acetate, the
organic layers were combined, washed with water, and dried over
anhydrous sodium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (available
from Merck Co., 9385, eluted with hexane:ethyl acetate=10:1) to
obtain 3.63 g (15.6 mmol, m.p. 102-104.degree. C.) of
3,4,6-trichloro-5-(chloromethyl)pyridazine.
(2) 3,6-Dichloro-4-methoxy-5-(methoxymethyl)pyridazine
In methanol (50 ml) was added 2.32 g (10.0 mmol) of
3,4,6-trichloro-5-(chloromethyl)pyridazine obtained in (1) and the
mixture was heated to make a solution. Then, the solution was
cooled to -60.degree. C. and a methanol solution of sodium
methoxide (prepared from 0.23 g of sodium and 5 mL of methanol,
10.0 mmol) was added dropwise to the solution. The solution was
stirred at -10.degree. C. for 2 hours and 30 minutes, and a
methanol solution of sodium methoxide (prepared from 0.23 g of
sodium and 5 mL of methanol, 10.0 mmol) was further added dropwise
to the solution. After stirring for 2 hours at -10.degree. C., and
the mixture was allowed to stand at room temperature overnight. The
reaction mixture was concentrated, and the residue was purified by
silica gel column chromatography (available from Merck Co., 9385,
eluted with hexane:ethyl acetate=5:1) to obtain 1.85 g (8.30 mmol,
Yield: 83.0%, m.p. 28-32.degree. C.) of
3,6-dichloro-4-methoxy-5-(methoxymethyl)pyridazine.
(3)
3-Chloro-5-methoxy-4-(methoxymethyl)-6-(2-methylphenoxy)pyridazine(Ste-
p D-1)
432 mg (4.00 mmol) of 2-methylphenol, methanol (20 mL) and 92 mg
(4.0 mmol) of sodium were mixed, and the mixture was stirred at
room temperature until sodium was disappeared. Methanol in the
mixture was distilled off, 50 mL of toluene was added to the
residue and the mixture was refluxed. The mixture was cooled in an
ice bath, a toluene solution (10 mL) containing 892 mg (4.00 mmol)
of 3,6-dichloro-4-methoxy-5-(methoxymethyl)pyridazine obtained in
(2) was added dropwise to the mixture, and the resulting mixture
was refluxed for 3 hours. The reaction mixture was allowed to stand
at room temperature overnight, washed with water, and then with
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (First time; available from Merck Co., 9385, eluted
with hexane:ethyl acetate=5:1. Second time; available from Merck
Co., 9385, eluted with hexane:ethyl acetate=8:1) to obtain 0.487 g
(1.65 mmol, Yield: 41.3%) of
3-chloro-5-methoxy-4-(methoxymethyl)-6-(2-methylphenoxy)pyridazine
and 0.266 g (0.902 mmol, Yield: 22.6%) of
3-chloro-4-methoxy-5-(methoxymethyl)-6-(2-methylphenoxy)pyridazine.
(4) 6-Chloro-5-(methoxymethyl)-3-(2-methylphenoxy)-4-pyridazinol
(Compound No. 2378, Step D-2)
0.354 g (1.20 mmol) of
3-chloro-5-methoxy-4-(methoxymethyl)-6-(2-methylphenoxy)pyridazine
obtained in (3), 1,4-dioxane (2 mL), 62 mg (1.49 mmol) of 96%
sodium hydroxide and water (8 mL) were mixed, and the mixture was
stirred at room temperature for 2 days, and further for 3 hours
under reflux. Hydrochloric acid was added to the reaction mixture
to make a pH 1, and then, the mixture was extracted with ethyl
acetate. The organic layers were combined, washed with water, and
dried over anhydrous sodium sulfate. The solvent was removed to
obtain 0.336 g (1.20 mmol, Yield: 100%) of
6-chloro-5-(methoxymethyl)-3-(2-methylphenoxy)-4-pyridazinol
(Compound No. 2378).
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 8.92 (1H, brs),
7.45-6.80 (4H, m), 4.39 (2H, s), 3.25 (3H, s), 2.25 (3H, s).
Melting point (.degree. C.): 123-126.
EXAMPLE 31
Ethyl
6-(2-tert-butylphenoxy)-3-chloro-5-hydroxy-4-pyridazinecarboxylate
(Compound No. 2386)
(1) 3-(2-Tert-butylphenoxy)-6-chloro-4-methoxypyridazine
5.87 g (39.1 mmol) of 2-tert-butylphenol, dimethylsulfoxide (80 mL)
and 4.38 g (39.0 mmol) of potassium t-butoxide were mixed, and the
mixture was stirred at room temperature for 20 minutes. To the
mixture was added a dimethylsulfoxide solution (60 mL) containing
6.92 g (38.7 mmol) of 3,6-dichloro-4-methoxypyridazine, and the
resulting mixture was stirred at room temperature for 40 minutes,
and at 80.degree. C. for 45 minutes. The reaction mixture was
poured into a saturated aqueous ammonium chloride solution, and
extracted with ethyl acetate. The organic layers were combined,
washed with water, and then, with brine, and dried over anhydrous
sodium sulfate. The solvent was removed, and the residue was
purified by silica gel column chromatography (available from Merck
Co., 9385, hexane:ethyl acetate, gradient) to obtain 2.66 g (9.09
mmol, Yield: 23.5%) of
3-(2-tert-butylphenoxy)-6-chloro-4-methoxypyridazine and 1.82 g
(6.22 mmol, Yield: 16.1%) of
6-(2-tert-butylphenoxy)-3-chloro-4-methoxypyridazine.
(2) Ethyl
6-(2-tert-butylphenoxy)-3-chloro-5-methoxy-4-pyridazinecarboxyla-
te (Step G-1)
In dry tetrahydrofuran (26 mL) was dissolved 783 mg (2.68 mmol) of
3-(2-tert-butylphenoxy)-6-chloro-4-methoxypyridazine obtained in
(1). The solution was cooled to -78.degree. C., 1.20 mL (2.80 mmol)
of a n-butyl lithium-hexane solution (2.33M) was added to the
solution and the resulting mixture was stirred for 20 minutes. To
the mixture was added 0.330 mL (3.45 mmol) of ethyl
chlorocarbonate, and the resulting mixture was stirred at the same
temperature for 30 minutes. The reaction mixture was poured into a
saturated aqueous ammonium chloride solution, and extracted with
ether. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous sodium sulfate. The
solvent was removed, and the obtained residue was purified by
silica gel column chromatography (eluted with hexane:ethyl
acetate=5:1) to obtain 603 mg (1.65 mmol, Yield: 61.6%) of ethyl
6-(2-tert-butylphenoxy)-3-chloro-5-methoxy-4-pyridazinecarboxylate.
(3) Eethyl
6-(2-tert-butylphenoxy)-3-chloro-5-hydroxy-4-pyridazinecarboxyl-
ate (Compound No. 2386, Step G-2)
419 mg (1.15 mmol) of ethyl
6-(2-tert-butylphenoxy)-3-chloro-5-methoxy-4-pyridazinecarboxylate
obtained in (2), 1,4-dioxane, 1 mol/L aqueous sodium hydroxide
solution (2.0 mL, 2.0 mmol) and dimethylsulfoxide (2.0 mL) were
mixed, and the mixture was stirred at room temperature for 2 hours
and 30 minutes, and at 80.degree. C. for 4 hours and 30 minutes.
After allowing to stand for cooling, the reaction mixture was made
acidic with hydrochloric acid, and extracted with dichloromethane.
The organic layers were combined, washed with brine, and dried over
anhydrous sodium sulfate. The solvent was removed, and the residue
was purified by silica gel column chromatography to obtain 337 mg
(0.960 mmol, Yield: 83.5%) of ethyl
6-(2-tert-butylphenoxy)-3-chloro-5-hydroxy-4-pyridazinecarboxylate
(Compound No. 2386). Appearance: amorphous.
EXAMPLE 32
3,6-Bis(2-methylphenoxy)-4-pyridazinol (Compound No. 2395)
(1) 3-chloro-5-methoxy-4,6-bis(2-methylphenoxy)pyridazine (Step
D-1)
In toluene (100 mL) was dissolved 5.32 g (49.3 mmol) of
2-methylphenol, and 1.13 g (49.1 mmol) of sodium, and then, 5.80 g
(27.2 mmol) of 3,4,6-trichloro-5-methoxypyridazine were added to
the solution and the resulting mixture was stirred for 4 hours
under reflux. The reaction mixture was poured into ice-cold water,
and extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
sodium sulfate. The solvent was removed, and the residue was
purified by silica gel column chromatography (hexane:ethyl acetate,
gradient) and recrystallized from isopropyl ether to obtain 3.0 g
(8.4 mmol, Yield: 31%) of
3-chloro-5-methoxy-4,6-bis(2-methylphenoxy)pyridazine.
(2) 6-Chloro-3,5-bis(2-methylphenoxy)-4-pyridazinol (Compound No.
2395, Step D-2)
0.72 g (2.0 mmol) of
3-chloro-5-methoxy-4,6-bis(2-methylphenoxy)pyridazine obtained in
(1) was added to a mixture comprising 0.60 mL (4.7 mmol) of
trimethylsilyl chloride, 0.60 g (4.0 mmol) of sodium iodide and
acetonitrile (15ml), and the resulting mixture was stirred
overnight. The reaction mixture was poured into ice-cold water, and
extracted with methylene chloride. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous sodium sulfate. The solvent was removed, and the residue
was purified by silica gel column chromatography (chloroform:
methanol, gradient) to obtain 0.45 g (1.3 mmol, Yield: 65%) of
6-chloro-3,5-(2-methylphenoxy)-4-pyridazinol (Compound No.
2395).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.32-7.05 (7H, m),
6.91 (1H, br.d, J=7.3 Hz), 2.29 (3H, s), 2.19 (3H, s). Melting
point (.degree. C.): 110-115.
EXAMPLE 33
3-(2-tert-Butylphenoxy)-6-chloro-5-(trimethylsilyl)-4-pyridazinol
(Compound No. 2405)
(1)
3-(2-tert-Butylphenoxy)-6-chloro-4-methoxy-5-(trimethylsilyl)pyridazin-
e(Step G-1)
In dry tetrahydrofuran (15 mL) was dissolved 498 mg (1.70 mmol) of
3-(2-tert-butylphenoxy)-6-chloro-4-methoxypyridazine obtained in
Example 31 (1), the solution was cooled to -78.degree. C., 1.10 mL
(1.87 mmol) of a n-butyl lithium-hexane solution (1.70M) was added
to the solution and the resulting mixture was stirred for 20
minutes. To the mixture was added 0.370 mL (2.91 mmol) of
trimethylsilyl chloride, and the resulting mixture was stirred at
the same temperature for 10 minutes. The reaction mixture was
poured into a saturated aqueous ammonium chloride solution,
extracted with ether. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the obtained residue was
purified by silica gel column chromatography to obtain 596 mg (1.63
mmol, Yield: 95.9%) of
3-(2-tert-butylphenoxy)-6-chloro-4-methoxy-5-(trimethylsilyl)py-
ridazine.
(2)
3-(2-tert-Butylphenoxy)-6-chloro-5-(trimethylsilyl)-4-pyridazinol
(Compound No. 2405, Step G-2)
0.17 g (1.1 mmol) of sodium iodide, 0.14 mL (1.1 mmol) of
trimethylsilyl chloride and acetonitrile (3.5 mL) were mixed, and
to the mixture was added with stirring 340 mg (0.932 mmol) of
3-(2-tert-butylphenoxy)-6-chloro-4-methoxy-5-(trimethylsilyl)pyridazine
obtained in (1), and the resulting mixture was stirred at room
temperature for 1 hour and 35 minutes. The reaction mixture was
poured into a saturated aqueous sodium sulfite solution, and
ice-cold diluted hydrochloric acid was added to the mixture. The
mixture was extracted with ethyl acetate, the organic layers were
combined and washed with brine. The solvent was removed, and the
residue was purified by silica gel column chromatography to obtain
275 mg (0.783 mmol, Yield: 84.0%) of
3-(2-tert-butylphenoxy)-6-chloro-5-(trimethylsilyl)-4-pyridazinol
(Compound No. 2405).
.sup.1H-NMR (90 MHz, CDCl.sub.3) .delta. ppm: 10.12 (1H, brs),
7.39-6.75 (4H, m), 1.24 (9H, s), 0.31 (9H, s). Melting point
(.degree. C.): 160-163.
EXAMPLE 34
6-Bromo-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 2411)
(1) 5-chloro-6-(2-methylphenoxy)-3-pyridazinol (Step P-1)
A mixture comprising 578 mg (2.27 mmol) of
4,6-dichloro-3-(2-methylphenoxy)pyridazine obtained in Example 1
(2), acetic acid (10 mL) and 0.45 g (4.6 mmol) of potassium acetate
was refluxed for 5 hours. The reaction mixture was allowed to stand
for cooling, and after adding 50 mL of water, the mixture was
extracted with ethyl acetate. The organic layers were combined, and
washed successively with water and brine. After drying over
anhydrous sodium sulfate, the solvent was removed to obtain 461 mg
(1.95 mmol, Yield: 85.9%) of
5-chloro-6-(2-methylphenoxy)-3-pyridazinol.
(2) 4,6-Dibromo-3-(2-methylphenoxy)pyridazine (Step P-2)
151 mg (0.637 mmol) of 5-chloro-6-(2-methylphenoxy)-3-pyridazinol
obtained in (1), chloroform(3 mL) and 913 mg (3.18 mmol) of
phosphorus oxybromide were mixed, and the mixture was refluxed for
5 hours. The reaction mixture was allowed to stand for cooling,
water and dichloromethane were added to the mixture and the
resulting mixture was stirred at room temperature for 1 hour. The
mixture was extracted with dichloromethane. The organic layers were
combined, and washed successively with water and brine. After
drying over anhydrous sodium sulfate, the solvent was removed. The
obtained residue was purified by silica gel column chromatography
to obtain 176 mg (0.512 mmol, Yield: 80.4%) of
4,6-dibromo-3-(2-methylphenoxy)pyridazine.
(3) 6-Bromo-3-(2-methylphenoxy)-4-pyridazinol (Compound No. 2411,
Step P-3)
In dimethylsulfoxide (3 mL) was dissolved 114 mg (0.331 mmol) of
4,6-dibromo-3-(2-methylphenoxy)pyridazine obtained in (2), 0.80 mL
(1.6 mmol) of 2 mol/L aqueous sodium hydroxide solution was added
to the solution, and the resulting mixture was stirred at room
temperature for 3 hours. Water was added to the reaction mixture,
and the resulting mixture was washed with ethyl acetate. The
aqueous layer was made acidic with 4 mol/L hydrochloric acid, and
extracted with ethyl acetate. The organic layers were combined,
washed with brine and dried over anhydrous sodium sulfate. The
solvent was removed, and the residue was washed with a mixed
solvent of ethyl acetate-ether to obtain 56.0 mg (0.199 mmol,
Yield: 60.1%) of 6-bromo-3-(2-methylphenoxy)-4-pyridazinol
(Compound No. 2411).
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.35-7.05 (4H, m),
6.82 (1H, brs), 2.10 (3H, s). Melting point (.degree. C.):
197-198.
EXAMPLE 35
6-Cyclopropyl-3-(2-methylphenoxy)-4-pyridazinol (Compound No.
2423)
(1) 6-Cyclopropyl-4-methoxy-3-(2-methylphenoxy)pyridazine (Step
L-1)
To a tetrahydrofuran solution (2.94 mL) containing of
9-borabicyclo[3.3.1]nonane (0.5 mol/l, 1.47 mmol) was added 87.5 mg
(0.735 mmol) of propargyl bromide, and the resulting mixture was
refluxed for 2 hours. The reaction mixture was cooled to room
temperature, 0.74 mL (2.2 mmol) of 3 mol/L aqueous sodium hydroxide
solution was added to the mixture, and the resulting mixture was
stirred at room temperature for 70 minutes. To the mixture were
successively added 168 mg (0.669 mmol) of
6-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in
Example 2 (1) and 38.7 mg (0.00334 mmol) of
tetrakis(triphenylphosphine)-palladium, and the resulting mixture
was refluxed overnight. The reaction mixture was allowed to stand
for cooling, water was added to the mixture, and the resulting
mixture was extracted with ethyl acetate. The organic layers were
combined, and washed successively with water and brine. After
drying over anhydrous sodium sulfate, the solvent was removed. The
obtained residue was purified by silica gel column chromatography
to obtain 121 mg (0.473 mmol, Yield: 70.1%) of
6-cyclopropyl-4-methoxy-3-(2-methylphenoxy)pyridazine.
(2) 6-Cyclopropyl-3-(2-methylphenoxy)-4-pyridazinol (Compound No.
2423, Step L-2)
In dimethylsulfoxide (2 mL) was dissolved 45.6 mg (0.479 mmol) of
2-hydroxypyridine, 53.8 mg (0.480 mmol) of potassium tert-butoxide
was added the solution at room temperature, and the resulting
mixture was stirred at room temperature for 10 minutes. To the
mixture was added a dimethylsulfoxide (1 mL) solution containing
112 mg (0.438 mmol) of
6-cyclopropyl-4-methoxy-3-(2-methylphenoxy)-pyridazine obtained in
(1), and the resulting mixture was stirred at 60.degree. C. for 5
hours, and at 80.degree. C. for 15 hours. Moreover, 45.6 mg (0.479
mmol) of 2-hydroxypyridine and then 53.8 mg (0.480 mmol) of
potassium tert-butoxide were additionally added to the mixture, and
the resulting mixture was stirred at 80.degree. C. for 4 hours and
30 minutes. The reaction mixture was allowed to stand for cooling,
water was added to the mixture, and and the resulting mixture was
washed with ethyl acetate. The aqueous layer was made acidic with 4
mol/L hydrochloric acid, and extracted with ethyl acetate. The
organic layers were combined, and washed successively with water
and brine. After drying over anhydrous sodium sulfate, the solvent
was removed. The obtained residue was purified by preparative
thin-layer chromatography (available from Merck Co., 1.05744,
developed by ethyl acetate) to obtain 28.6 mg (0.118 mmol, Yield:
26.9%) of 6-cyclopropyl-3-(2-methylphenoxy)-4-pyridazinol (Compound
No. 2423).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.30-7.01 (4H, m),
6.19 (1H, s), 1.98-1.82 (1H, m), 1.23-1.12 (2H, m), 0.99-0.88 (2H,
m). Melting point (.degree. C.): 214-215.
EXAMPLE 36
3-(2-Methylphenoxy)-6-vinyl-4-pyridazinol (Compound No. 2436)
(1) 4-Methoxy-3-(2-methylphenoxy)-6-vinylpyridazine (Step L-1)
In toluene (2 mL) was dissolved 123 mg (0.490 mmol) of
6-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in
Example 2 (1), 246 mg (0.776 mmol) of tributyl-(vinyl)tin, and
then, 119 mg (0.103 mmol) of tetrakis(triphenylphosphine)palladium
were successively added to the solution at room temperature, and
the resulting mixture was refluxed for 3 hours. The reaction
mixture was allowed to stand for cooling, ethyl acetate (5 mL),
water (3 mL) and sodium fluoride were added to the mixture, and the
resulting mixture was stirred for 30 minutes and allowed to stand
at at room temperature overnight. The mixture was filtered through
Celite, ethyl acetate was added to the filtrate, then the organic
layer was separated and washed with brine. After drying over
anhydrous sodium sulfate, the solvent was removed. The obtained
residue was purified by silica gel column chromatography (eluted
with hexane:ethyl acetate=1:2) to obtain 105 mg (0.434 mmol, Yield:
88.6%) of 4-methoxy-3-(2-methylphenoxy)-6-vinylpyridazine.
(2) 3-(2-Methylphenoxy)-6-vinyl-4-pyridazinol (Compound No. 2436,
Step L-2)
In dimethylsulfoxide (1 mL) was dissolved 33.7 mg (0.354 mmol) of
2-hydroxypyridine, 39.7 mg (0.354 mmol) of potassium tert-butoxide
was added to the solution at room temperature, and the resulting
mixture was stirred at room temperature for 10 minutes. To the
mixture was added a dimethylsulfoxide (1 mL) solution containing
85.8 mg (0.354 mmol) of
4-methoxy-3-(2-methylphenoxy)-6-vinylpyridazine obtained in (1),
and the resulting mixture was stirred at room temperature overnight
and at 50.degree. C. for 4 hours and 30 minutes. The reaction
mixture was allowed to stand for cooling, water was added thereto,
and the resulting mixture was washed with ethyl acetate. The
aqueous layer was made acidic with 4 mol/L hydrochloric acid, and
extracted with ethyl acetate. The organic layers were combined,
dried over anhydrous sodium sulfate, and the solvent was removed.
The obtained residue was purified by silica gel column
chromatography (eluted with hexane:ethyl acetate=1:4) to obtain
51.7 mg (0.227 mmol, Yield: 64.1%) of
3-(2-methylphenoxy)-6-vinyl-4-pyridazinol (Compound No. 2436).
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.35-7.03 (4H, m),
6.56-6.43 (2H, m), 6.16 (1H, d, J=17.9 Hz), 6.16 (1H, d, J=11.4
Hz), 2.11 (3H, s). Melting point (.degree. C.): 195-197.
EXAMPLE 37
3-(2-Methylphenoxy)-6-(1-propenyl)-4-pyridazinol (Compound No.
2442)
(1) 6-Allyl-4-methoxy-3-(2-methylphenoxy)pyridazine (Step L-1)
In toluene (4 mL) was dissolved 200 mg (0.797 mmol) of
6-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in
Example 2 (1), 305 mg (0.921 mmol) of allyl-(tributyl)tin, and
then, 96.8 mg (0.0838 mmol) of
tetrakis-(triphenylphosphine)palladium were successively added to
the solution at room temperature, and the resulting mixture was
refluxed for 3 hours and 20 minutes. The reaction mixture was
allowed to stand at room temperature overnight, and then, ethyl
acetate, water and sodium fluoride were added to the mixture and
the resulting mixture was stirred for 2 hours. The mixture was
filtered through Celite, ethyl acetate was added to the filtrate,
then the organic layer was separated, and washed successively with
water and brine. After drying over anhydrous sodium sulfate, the
solvent was removed. The obtained residue was purified by silica
gel column chromatography (hexane:ethyl acetate, gradient) to
obtain 62.1 mg (0.243 mmol, Yield: 30.5%) of
6-allyl-4-methoxy-3-(2-methylphenoxy)pyridazine.
(2) 3-(2-Methylphenoxy)-6-(1-propenyl)-4-pyridazinol (Compound No.
2442, Step L-2)
In dimethylsulfoxide (2 mL) was dissolved 25.3 mg (0.267 mmol) of
2-hydroxypyridine, 29.9 mg (0.267 mmol) of potassium tert-butoxide
was added to the solution at room temperature, and the resulting
mixture was stirred at room temperature for 10 minutes. To the
mixture was added a dimethylsulfoxide (3 mL) solution containing
62.1 mg (0.243 mmol) of
6-allyl-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in (1),
and the resulting mixture was stirred at 100.degree. C. for 8 hours
and at 130.degree. C. for 5 hours and 30 minutes. Moreover, 25.3 mg
(0.267 mmol) of 2-hydroxypyridine, and then, 29.9 mg (0.267 mmol)
of potassium tert-butoxide were additionally added to the mixture,
and the resulting mixture was stirred at 130.degree. C. for 5
hours. The reaction mixture was allowed to stand for cooling, and
after adding water, the mixture was washed with ethyl acetate. The
aqueous layer was made acidic with 4 mol/L hydrochloric acid, and
extracted with ethyl acetate. The organic layers were combined,
dried over anhydrous sodium sulfate, and the solvent was removed.
The obtained residue was purified by preparative thin-layer
chromatography (available from Merck Co., 1.05744, 3 plates were
used, developed by ethyl acetate) to obtain 21.3 mg (0.0880 mmol,
Yield: 36.2%) of 3-(2-methylphenoxy)-6-(1-propenyl)-4-pyridazinol
(Compound No. 2442).
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.32-7.03 (4H, m),
6.75-6.60 (1H, m), 6.44 (1H, s), 6.22-6.10 (1H, m), 2.10 (3H s),
1.86 (3H, br.d, J=6.6 Hz). Melting point (.degree. C.):
208-210.
EXAMPLE 38
6-(2,6-Dimethylphenoxy)-5-hydroxy-3-pyridazinecarbonitrile
(Compound No. 2453)
(1) 6-Chloro-3-(2,6-dimethylphenoxy)-4-methoxypyridazine 1-oxide
(Step K-1)
3.42 g (12.9 mmol) of
6-chloro-3-(2,6-dimethylphenoxy)-4-methoxypyridazine,
dichloromethane (110 mL) and 3.34 g (15.4 mmol) of 80%
m-chloroperbenzoic acid were mixed, and the mixture was stirred at
at room temperature for 16 days. The reaction mixture was poured
into ice-cold saturated aqueous sodium sulfite solution, and
extracted with dichloromethane. The organic layers were combined,
washed successively with a saturated aqueous sodium hydrogen
carbonate solution, water and brine, and dried over anhydrous
sodium sulfate. The solvent was removed, and the residue was
purified by silica gel column chromatography to obtain 2.06 g (7.33
mmol, Yield: 56.8%) of
6-chloro-3-(2,6-dimethylphenoxy)-4-methoxypyridazine 1-oxide.
(2) 3-(2,6-Dimethylphenoxy)-4-methoxypyridazine 1-oxide (Step
K-2)
6.00 g (21.4 mmol) of
6-chloro-3-(2,6-dimethylphenoxy)-4-methoxypyridazine 1-oxide
obtained in (1), methanol (200 mL), 3.0 mL of triethylamine,
acetone (5 mL) and 0.5 g of 5% palladium carbon were mixed, and the
mixture was shaked by using a Parr reducing device under a hydrogen
pressure of 3.5 atm for 2 hours. The reaction mixture was filtered,
and the filtrate was concentrated. Water was added to the residue,
and the mixture was extracted with chloroform. The organic layers
were combined, washed with brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the residue was crystallized
from an ether-dichloromethane mixed solvent to obtain 4.32 g (17.6
mmol, Yield: 82.2%) of 3-(2,6-dimethylphenoxy)-4-methoxypyridazine
1-oxide.
(3) 6-(2,6-Dimethylphenoxy)-5-methoxy-3-pyridazinecarbonitrile
(Step M-1)
In dry N,N-dimethylformamide (15 mL) was dissolved 0.720 g (2.92
mmol) of 3-(2,6-dimethylphenoxy)-4-methoxypyridazine 1-oxide
obtained in (2), 1.10 mL (8.25 mmol) of trimethylsilylcyanide and
2.00 mL (14.4 mmol) of triethylamine were added to the solution,
and the resulting mixture was stirred at 90.degree. C. for 1 hour
and 30 minutes. The reaction mixture was poured into a saturated
aqueous ammonium chloride solution, and extracted with ethyl
acetate. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous sodium sulfate. The
solvent was removed, and the residue was purified by silica gel
column chromatography to obtain 0.675 g (2.65 mmol, Yield: 90.8%)
of 6-(2,6-dimethylphenoxy)-5-methoxy-3-pyridazinecarbonitrile.
(4) 6-(2,6-Dimethylphenoxy)-5-hydroxy-3-pyridazinecarbonitrile
(Compound No. 2453, Step M-2)
In acetonitrile (5 mL) was dissolved 0.500 g (1.96 mmol) of
6-(2,6-dimethylphenoxy)-5-methoxy-3-pyridazinecarbonitrile obtained
in (3), 0.300 mL (2.36 mmol) of trimethylsilyl chloride and 0.350 g
(2.33 mmol) of sodium iodide were added to the solution, and the
resulting mixture was stirred at room temperature. 5 mL of
acetonitrile was additionally added and the resulting mixture was
stirred for 1 hour, then, 3 mL of 1,4-dioxane was added thereto,
and the resulting mixture was stirred overnight. The reaction
mixture was poured into an aqueous sodium sulfite solution, and
made acidic by adding 1 mol/L hydrochloric acid. The resulting
mixture was extracted with dichloromethane, washed with brine, and
dried over anhydrous sodium sulfate. The solvent was removed, and
the residue was purified by silica gel column chromatography to
obtain 0.121 g (0.502 mmol, Yield: 25.6%) of
6-(2,6-dimethylphenoxy)-5-hydroxy-3-pyridazinecarbonitrile
(Compound No. 2453).
.sup.1H-NMR (90 MHz, CDCl.sub.3) .delta. ppm: 11.3 (1H, brs),
7.09-6.99 (4H, m), 1.90 (6H, s). Appearance: amorphous.
EXAMPLE 39
1-[5-Hydroxy-6-(2-methylphenoxy)-3-pyridazinyl]-ethanone (Compound
No. 2455)
(1) 6-(1-Ethoxyvinyl)-4-methoxy-3-(2-methylphenoxy)-pyridazine
(Step L-1)
In toluene (6.5 mL) was dissolved 321 mg (1.28 mmol) of
6-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in
Example 2 (1), 534 mg (1.48 mmol) of (1-ethoxyvinyl)(tributyl)tin,
then 155.3 mg (0.134 mmol) of tetrakis(triphenylphosphine)palladium
were successively added to the solution at room temperature, and
the resulting mixture was refluxed for 3 hours and 20 minutes. The
reaction mixture was allowed to stand at room temperature
overnight, then, ethyl acetate, water and sodium fluoride were
added to the mixture and the resulting mixture was stirred for 2
hours. The mixture was filtered through Celite, ethyl acetate was
added to the filtrate, and the organic layer was separated, and
washed successively with water and brine. After drying over
anhydrous sodium sulfate, the solvent was removed. The obtained
residue was purified by silica gel column chromatography
(hexane:ethyl acetate, gradient) to obtain 51.8 mg (0.181 mmol,
Yield: 14.1%) of
6-(1-ethoxyvinyl)-4-methoxy-3-(2-methylphenoxy)pyridazine.
(2) 1-[5-Hydroxy-6-(2-methylphenoxy)-3-pyridazinyl]ethanone
(Compound No. 2455, Step L-2)
In dimethylsulfoxide (2 mL) was dissolved 18.4 mg (0.194 mmol) of
2-hydroxypyridine, 21.7 mg (0.194 mmol) of potassium tert-butoxide
was added to the solution at room temperature, and the resulting
mixture was stirred at room temperature for 10 minutes. To the
mixture was added a dimethylsulfoxide (3 mL) solution containing
50.4 mg (0.176 mmol) of
6-(1-ethoxyvinyl)-4-methoxy-3-(2-methylphenoxy)-pyridazine obtained
in (1), and the resulting mixture was stirred at 100.degree. C. for
8 hours and at 130.degree. C. for 5 hours and 30 minutes. Moreover,
18.4 mg (0.194 mmol) of 2-hydroxypyridine, then 21.7 mg (0.194
mmol) of potassium tert-butoxide were additionally added to the
mixture, and the resulting mixture was stirred at 130.degree. C.
for 2 hours. The reaction mixture was allowed to stand for cooling,
and after adding water, and the mixture was washed with ethyl
acetate. The aqueous layer was made acidic with 4 mol/L
hydrochloric acid, and extracted with ethyl acetate. The organic
layers were combined, dried over anhydrous sodium sulfate, and the
solvent was removed. The obtained residue was purified by
preparative thin-layer chromatography (available from Merck Co.,
1.05744, 3 plates were used, developed by ethyl acetate) to obtain
28.5 mg (0.117 mmol, Yield: 66.5%) of
1-[5-hydroxy-6-(2-methylphenoxy)-3-pyridazinyl]ethanone (Compound
No. 2455).
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.48-7.05 (5H, m),
2.58 (3H, s), 2.10 (3H, s). Melting point (.degree. C.):
182-185.
EXAMPLE 40
3-(2-Methylphenoxy)-6-phenyl-4-pyridazinol (Compound No. 2464)
(1) 4-Methoxy-3-(2-methylphenoxy)-6-phenylpyridazine (Step L-1)
210 mg (0.837 mmol) of
6-chloro-4-methoxy-3-(2-methylphenoxy)pyridazine obtained in
Example 2 (1), toluene (4 mL) and water (0.5 mL) were mixed, 161 mg
(1.32 mmol) of phenylboronic acid, 365 mg (2.64 mmol) of potassium
carbonate and 102 mg (0.0879 mmol) of
tetrakis(triphenylphosphine)palladium were successively added to
the mixture at room temperature, and the resulting mixture was
refluxed for 2 hours and 50 minutes. The reaction mixture was
allowed to stand at room temperature overnight, the mixture was
filtered through Celite, and ethyl acetate and water were added to
the filtrate. The organic layer was separated, washed with brine.
After drying over anhydrous sodium sulfate, the solvent was
removed. The obtained residue was purified by silica gel column
chromatography (eluted with hexane:ethyl acetate=3:1) to obtain 146
mg (0.500 mmol, Yield: 59.7%) of
4-methoxy-3-(2-methylphenoxy)-6-phenylpyridazine.
(2) 3-(2-Methylphenoxy)-6-phenyl-4-pyridazinol (Compound No. 2464,
Step L-2)
In dimethylsulfoxide (1.5 mL) was dissolved 91.9 mg (0.966 mmol) of
2-hydroxypyridine, 95.4 mg (0.850 mmol) of potassium tert-butoxide
was added to the solution at room temperature, and the resulting
mixture was stirred at room temperature for 10 minutes. To the
mixture was added a dimethylsulfoxide (1 mL) solution containing
82.8 mg (0.283 mmol) of
4-methoxy-3-(2-methylphenoxy)-6-phenylpyridazine obtained in (1),
and the resulting mixture was stirred at 60.degree. C. for 3 hours.
The reaction mixture was allowed to stand for cooling, and after
adding water, the mixture was washed with ethyl acetate. The
aqueous layer was made acidic with 4 mol/L hydrochloric acid, and
extracted with ethyl acetate. The organic layers were combined,
washed with brine, and dried over anhydrous sodium sulfate. The
solvent was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from Merck Co.,
1.05744, 3 plates were used, developed by ethyl acetate) to obtain
70.8 mg (0.255 mmol, Yield: 90.1%) of
3-(2-methylphenoxy)-6-phenyl-4-pyridazinol (Compound No. 2464).
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.78-7.66 (2H, m),
7.58-7.48 (3H, m), 7.35-7.08 (4H, m), 6.69 (1H, s), 2.15 (3H s).
Melting point (.degree. C.): 236-237.
EXAMPLE 41
3,6-Bis(2-fluorophenoxy)-4-pyridazinol (Compound No. 2485)
(1) 3,6-Bis(2-fluorophenoxy)pyridazine
In dimethylsulfoxide (20 mL) was dissolved 2.69 g (24.0 mmol) of
2-fluorophenol, and 2.69 g (24.0 mmol) of potassium tert-butoxide
was added to the solution at room temperature. To the mixture was
added 1.49 g (10.0 mmol) of 2,6-dichloropyridazine, and the
resulting mixture was stirred at 100.degree. C. for 3 hours. The
reaction mixture was allowed to stand for cooling, pouted into
ice-cold water, and extracted with ethyl acetate. The organic
layers were combined, washed successively with 1 mol/L aqueous
sodium hydroxide solution, water and brine, and dried over
anhydrous sodium sulfate. The solvent was removed, the obtained
residue was washed with a hot hexane, and then with a hot isopropyl
ether to obtain 1.71 g (5.70 mmol, Yield: 57.0%) of
3,6-bis(2-fluorophenoxy)pyridazine.
(2) 3,6-Bis(2-fluorophenoxy)pyridazine 1-oxide (Step C-1)
In dry dichloromethane (40 mL) was dissolved 4.14 g (13.8 mmol) of
3,6-bis(2-fluorophenoxy)pyridazine obtained in (1), 3.19 g (14.8
mmol) of 80% m-chloroperbenzoic acid was added to the solution, and
the resulting mixture was stirred at room temperature for 7 days.
The reaction mixture was poured into ice-cold 1 mol/L aqueous
sodium hydroxide solution, and extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the obtained residue was purified by silica gel column
chromatography (eluted with hexane:ethyl acetate=3:1) to obtain
2.24 g (7.09 mmol, Yield: 51.4%) of
3,6-bis(2-fluorophenoxy)pyridazine 1-oxide.
(3) 4-Chloro-3,6-bis(2-fluorophenoxy)pyridazine (Step C-2)
2.20 g (6.96 mmol) of 3,6-bis(2-fluorophenoxy)pyridazine 1-oxide
obtained in (2) and 50 mL of phosphorus oxychloride were mixed, and
the mixture was stirred at 90.degree. C. for 1 hour. The reaction
mixture was allowed to stand for cooling, poured into ice-cold
water, and extracted with ethyl acetate. The organic layers were
combined, washed successively with 1 mol/L aqueous sodium hydroxide
solution, water and brine, and dried over anhydrous sodium sulfate.
The solvent was removed, and the obtained residue was purified by
silica gel column chromatography (hexane:ethyl acetate=10:1) to
obtain 1.95 g (5.82 mmol, Yield: 83.6%) of
4-chloro-3,6-bis(2-fluorophenoxy)pyridazine.
(4) 3,6-Bis(2-fluorophenoxy)-4-methoxypyridazine (Step C-3)
In methanol (20 mL) was dissolved 1.44 g (4.30 mmol) of
4-chloro-3,6-bis(2-fluorophenoxy)pyridazine obtained in (3), 0.206
g (4.72 mmol) of 55% sodium hydride was added to the solution, and
the resulting mixture was stirred at 60.degree. C. for 1 hour. The
reaction mixture was allowed to stand for cooling, poured into
ice-cold water, and extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine, and
dried over anhydrous sodium sulfate. The solvent was removed, and
the obtained residue was purified by silica gel column
chromatography (eluted with hexane:ethyl acetate=10:1) to obtain
1.03 g (3.12 mmol, Yield: 72.6%) of
3,6-bis(2-fluorophenoxy)-4-methoxypyridazine.
(5) 3,6-Bis(2-fluorophenoxy)-4-pyridazinol (Compound No. 2485, Step
C-4)
450 mg (1.36 mmol) of 3,6-bis(2-fluorophenoxy)-4-methoxypyridazine
obtained in (4), 77 mg (1.85 mmol) of 96% sodium hydroxide,
dimethylsulfoxide (5 mL) and water (1 mL) were mixed, and the
mixture was stirred at 90.degree. C. for 2 hours. The reaction
mixture was poured into ice-cold water, and made acidic with
hydrochloric acid. The mixture was extracted with ethyl acetate,
washed with water, and dried over anhydrous sodium sulfate. The
solvent was removed to obtain 0.380 g (1.20 mmol, Yield: 88.2%) of
3,6-bis(2-fluorophenoxy)-4-pyridazinol (Compound No. 2485).
.sup.1H-NMR. (60 MHz, DMSO-d.sub.6) .delta. ppm: 7.60-7.08 (8H, m),
6.34 (1H, brs). Melting point (.degree. C.): 228.
EXAMPLE 42
(2,4-Dichlorophenyl)(5-{[5-hydroxy-6-(2-methylphenoxy)-3-pyridazinyl]oxy}--
1,3-dimethyl-1H-pyrazol-4-yl)methanone (Compound No. 2506)
(1)
(5-{[5-Chloro-6-(2-methylphenoxy)-3-pyridazinyl]oxy}-1,3-dimethyl-1H-p-
yrazol-4-yl)(2,4-dichlorophenyl)meth
109 mg (0.382 mmol) of
(2,4-dichlorophenyl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)methanone,
1.62 g (6.35 mmol) of 4,6-dichloro-3-(2-methylphenoxy)pyridazine
obtained in Example 1 (2) and 107 mg (0.775 mmol) of potassium
carbonate were mixed, and the mixture was stirred at 130.degree. C.
for 14 hours. The reaction mixture was cooled up to room
temperature, and purified by silica gel column chromatography
(hexane:ethyl acetate, gradient) to obtain 155 mg (0.308 mmol,
Yield: 80.6%) of
(5-{[5-chloro-6-(2-methylphenoxy)-3-pyridazinyl]oxy}-1,3-dimethyl-1H-pyra-
zol-4-yl)(2,4-dichlorophenyl)methanone.
(2)
(2,4-Dichlorophenyl)(5-{[5-hydroxy-6-(2-methylphenoxy)-3-pyridazinyl]o-
xy}-1,3-dimethyl-1H-pyrazol-4-yl)met (Compound No. 2506, A-3
Step)
12.3 mg (0.0244 mmol) of
(5-{[5-chloro-6-(2-methylphenoxy)-3-pyridazinyl]oxy}-1,3-dimethyl-1H-pyra-
zol-4-yl)(2,4-dichlorophenyl)methanone obtained in (1), 0.2 mL of
dimethylsulfoxide and 0.012 mL of 10% (W/V) aqueous sodium
hydroxide solution were mixed, and the mixture was stirred at room
temperature overnight. The reaction mixture was poured into
ice-cold water, made acidic by hydrochloric acid, and extracted
with ethyl acetate. The organic layers were combined, and dried
over anhydrous sodium sulfate. The solvent was distilled off and
the residue was purified by preparative thin-layer chromatography
(available from Merck Co., 1.05744, developed by
dichloromethane:methanol=10:1) to obtain 3.2 mg (0.00784 mmol,
Yield: 32%) of
(2,4-dichlorophenyl)(5-{[5-hydroxy-6-(2-methylphenoxy)-3-pyridazi-
nyl]oxy}-1,3-dimethyl-1H-pyrazol-4-yl)methanone (Compound No. 2506)
and 10.5 mg (0.0208 mmol, Yield: 85.4%) of
4-[{[5-chloro-6-(2-methylphenoxy)-3-pyridazinyl]oxy}-(2,4-dichlorophenyl)-
methylene]-2,5-dimethyl-2,4-dihydro-3H-pyrazol-3-one.
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.36-7.04 (7H, m),
6.20 (1H, brs), 3.64 (3H, s), 2.31 (3H, s), 2.20 (3H, s).
Appearance: amorphous.
Also, the following compounds were produced in accordance with the
above-mentioned Examples 1 to 42 or by the methods or in accordance
with the methods described in the following Examples 622 to
646.
EXAMPLE 43
3-Phenoxy-4-pyridazinol (Compound No. 1)
.sup.1H-NMR (90 MHz, DMSO-d.sub.6) .delta. ppm: 12.66 (1H, brs),
8.21 (1H, d, J=6.6 Hz), 7.09-7.54 (5H, m), 6.38 (1H, d, J=6.6 Hz).
Melting point (.degree. C.): 193.5.
EXAMPLE 44
6-Chloro-3-{2-[1-(methoxymethyl)cyclopropyl]phenoxy}-4-pyridazinol
(Compound No. 163)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.47-7.35 (1H, m),
7.32-7.02 (3H, m), 6.71 (1H, s), 3.47 (2H, s), 3.21 (3H, s),
0.80-0.70 (4H, m). Melting point (.degree. C.): 187-190.
EXAMPLE 45
3-(2-Isopropylphenoxy)-4-pyridazinol (Compound No. 6)
.sup.1H-NMR (90 MHz, DMSO-d.sub.6) .delta. ppm: 12.65 (1H, brs),
8.29 (2H, d, J=6.6 Hz), 7.49-6.98 (4H, m), 6.36 (1H, d, J=6.6 Hz),
3.20-2.89 (1H, m, J=6.6 Hz), 1.16 (6H, d, J=6.6 Hz). Melting point
(.degree. C.): 181.5-182.
EXAMPLE 46
6-Chloro-3-[2-(1-methoxycyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 202)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.50-7.10 (4H, m),
6.67 (1H, s), 3.03 (3H, s), 1.00-0.85 (4H, m). Melting point
(.degree. C.): 157-165.
EXAMPLE 47
2-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}-cyclopropanecarbonitri-
le (Compound No. 226)
Trans isomer:
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.40-7.10 (4H, m),
6.75 (1H, s), 2.65-2.50 (1H, m), 1.65-1.45 (3H, m). Melting point
(.degree. C.): 203-207.
Cis isomer:
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.40-7.15 (4H, m),
6.64 (1H, s), 2.59 (1H, q, J=8.4 Hz), 2.05-1.90 (1H, m), 1.67-1.40
(2H, m). Melting point (.degree. C.): 225-227.
EXAMPLE 48
6-Chloro-3-phenoxy-4-pyridazinol (Compound No. 123)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.60-7.00 (5H, m),
6.87 (1H, s). Melting point (.degree. C.): 222-224.
EXAMPLE 49
6-Chloro-3-(2-fluorophenoxy)-4-pyridazinol (Compound No. 124)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.50-7.05 (4H, m),
6.70 (1H, s). Melting point (.degree. C.): 210-212.
EXAMPLE 50
6-Chloro-3-(2-chlorophenoxy)-4-pyridazinol (Compound No. 125)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.70-7.10 (4H, m),
6.95 (1H, s). Melting point (.degree. C.): 208-212.
EXAMPLE 51
3-(2-Bromophenoxy)-6-chloro-4-pyridazinol (Compound No. 126)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.68 (1H, dd, J=7.5,
1.8 Hz), 7.53-7.10 (3H, m), 6.73 (1H, s). Melting point (.degree.
C.): 201-203.
EXAMPLE 52
6-Chloro-3-(2-iodophenoxy)-4-pyridazinol (Compound No. 127)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.89 (1H, dd, J=7.7,
1.5 Hz) 7.45 (1H, td, J=7.7, 1.5 Hz), 7.22 (1H, dd, J=7.7, 1.5 Hz),
7.04 (1H, td, J=7.7, 1.5 Hz), 6.74 (1H, s). Melting point (.degree.
C.): 216-217.
EXAMPLE 53
6-Chloro-3-[2-(2-ethoxycyclopropyl)phenoxy]-4-pyridazinol (Compound
No. 249)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.26-7.05 (4H, m),
6.68 (1H, s), 3.46 (1H, q, J=5.2 Hz), 3.30-3.15 (2H, m), 2.17-1.96
(1H, m), 1.10 (2H, dd, J=5.2 Hz, 8.5 Hz), 0.93 (3H, t, J=7.0 Hz).
Melting point (.degree. C.): 145-152.
EXAMPLE 54
6-Chloro-3-[2-(2,2-difluorocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 264)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.40-7.15 (4H, m),
6.72 (1H, s), 2.85-2.65 (1H, m), 1.90-1.65 (2H, s). Melting point
(.degree. C.): 215-216.
EXAMPLE 55
6-Chloro-3-(2-ethylphenoxy)-4-pyridazinol (Compound No. 130)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.35-7.15 (3H, m),
7.10-7.02 (1H, m), 6.70 (1H, s), 2.56 (2H, q, J=7.7 Hz), 1.17 (3H,
t, J=7.7 Hz). Melting point (.degree. C.): 217-218.
EXAMPLE 56
6-Chloro-3-(2-propylphenoxy)-4-pyridazinol (Compound No. 131)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.45-7.05 (4H, m),
6.90 (1H, s), 3.00-2.35 (2H, m), 1.95-1.26 (2H, m), 1.05-0.68 (3H,
m). Melting point (.degree. C.): 170-172.
EXAMPLE 57
6-Chloro-3-(2-isopropylphenoxy)-4-pyridazinol (Compound No.
132)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.60-7.00 (4H, m),
6.92 (1H, s), 3.11 (1H, septet, J=7.0 Hz), 1.18 (6H, d, J=7.0 Hz).
Melting point (.degree. C.): 183.
EXAMPLE 58
3-(2-Butylphenoxy)-6-chloro-4-pyridazinol (Compound No. 133)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 11.8 (1H, brs),
7.30-6.70 (4H, m), 6.53 (1H, s), 2.60-2.00 (2H, m), 1.80-0.60 (7H,
m). Melting point (.degree. C.): 149.5-150.
EXAMPLE 59
6-Chloro-3-(2-isobutylphenoxy)-4-pyridazinol (Compound No. 134)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 12.90 (1H, brs),
7.40-6.85 (4H, m), 6.50 (1H, s), 2.25 (2H, d, J=10.0 Hz), 2.20-1.45
(1H, m, J=10.0 Hz), 0.75 (6H, d, J=10.0 Hz). Melting point
(.degree. C.): 151.5-152.5.
EXAMPLE 60
3-(2-s-Butylphenoxy)-6-chloro-4-pyridazinol (Compound No. 135)
.sup.1H-NMR (60 MHz, CDCl.sub.3+DMF-d.sub.7) .delta. ppm: 7.35-6.80
(4H, m), 6.60 (1H, s), 3.05-2.50 (1H, m), 1.80-1.25 (2H, m), 1.13
(3H, d, J=6.2 Hz), 0.95-0.50 (3H, m). Melting point (.degree. C.):
158-159.
EXAMPLE 61
3-(2-tert-Butylphenoxy)-6-chloro-4-pyridazinol (Compound No.
136)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.55-6.85 (4H, m),
6.91 (1H, s), 5.32 (1H, brs), 1.35 (9H, s). Melting point (.degree.
C.): 215-216.
EXAMPLE 62
6-Chloro-3-(2-pentylphenoxy)-4-pyridazinol (Compound No. 137)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 11.70 (1H, brs),
7.40-6.80 (4H, m), 6.50 (1H, s), 2.60-2.20 (2H, m), 1.80-0.60 (9H,
m). Melting point (.degree. C.): 151.5-152.5.
EXAMPLE 63
6-Chloro-3-(2-hexylphenoxy)-4-pyridazinol (Compound No. 138)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.40-6.70 (4H, m),
6.53 (1H, s), 2.70-2.20 (2H, m), 2.00-0.60 (11H, m). Melting point
(.degree. C.): 118-118.5.
EXAMPLE 64
6-Chloro-3-[2-(2,2-dichlorocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 265)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.55-7.15 (4H, m),
6.69 (1H, s), 2.90 (1H, dd, J=11.0, 10.8 Hz), 2.05-1.85 (2H, m).
Melting point (.degree. C.): 158-163.
EXAMPLE 65
6-Chloro-3-[2-(2,2-dibromocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 266)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.41-7.36 (1H, m),
7.29-7.13 (3H, m), 6.71 (1H, s), 2.97-2.87 (1H, dd, J=11.0, 8.4
Hz), 2.21-2.01 (2H, m). Melting point (.degree. C.): 208-210
(decomposed).
EXAMPLE 66
6-Chloro-3-[2-(1-methylcyclopropyl)phenoxy]-4-pyridazinol (Compound
No. 144)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.40-7.35 (1H, m),
7.22-7.17 (2H, m), 6.99-6.94 (1H, m), 6.59 (1H, s), 1.25 (3H, s),
0.85-0.60 (2H, m), 0.60-0.45 (2H, m). Melting point (.degree. C.):
196-198.
EXAMPLE 67
6-Chloro-3-[2-(1-ethylcyclopropyl)phenoxy]-4-pyridazinol (Compound
No. 145)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.35-7.10 (3H, m),
6.98 (1H, br.d, J=7.3 Hz), 6.59 (1H, s), 1.50 (2H, q, J=7.0 Hz),
1.26 (3H, t, J=7.0 Hz), 0.67-0.50 (4H, m). Melting point (.degree.
C.): 162-165.
EXAMPLE 68
6-Chloro-3-{2-[1-(cyclopropyl)cyclopropyl]phenoxy}-4-pyridazinol
(Compound No. 151)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.35-7.29 (1H, m),
7.26-7.10 (2H m), 7.00-6.92 (1H, m), 6.58 (1H, s), 1.30-1.15 (1H,
m), 0.60-0.40 (4H, m), 0.27-0.15 (2H, m), 0.07-0.00 (2H, m).
Melting point (.degree. C.): 180-182.
EXAMPLE 69
1-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}-cyclopropanecarbonitri-
le (Compound No. 173)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.55-7.15 (5H, m),
1.65-1.20 (4H, m). Melting point (.degree. C.): 63-64.
EXAMPLE 70
6-Chloro-3-[2-(1-phenylcyclopropyl)phenoxy]-4-pyridazinol (Compound
No. 184)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.65-7.55 (1H, m),
7.28-7.20 (2H, m), 7.17-6.95 (6H, m), 6.41 (1H, s), 1.19 (4H, s).
Melting point (.degree. C.): 172-173.
EXAMPLE 71
6-Chloro-3-(2-isopropenylphenoxy)-4-pyridazinol (Compound No.
304)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.36-7.10 (4H, m),
6.66 (1H, s), 5.06 (1H, br.s), 5.02 (1H, br.s), 2.01 (3H, d, J=1.5
Hz). Melting point (.degree. C.): 187-188.
EXAMPLE 72
6-Chloro-3-[2-(2-methylcyclopropyl)phenoxy]-4-pyridazinol (Compound
No. 217)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.32-6.97 (4H, m),
6.82 (1H, brs), 1.89-1.78 (0.8H, m), 1.52-1.43 (0.2H, m), 1.05-0.60
(6H, m). Melting point (.degree. C.): 192-208.
EXAMPLE 73
6-Chloro-3-[2-(2-ethoxycyclopropyl)phenoxy]-4-pyridazinol (Compound
No. 249)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.30-7.05 (4H, m),
6.68 (1H, s), 3.51-3.15 (3H, m), 2.07-1.95 (1H, m), 1.13-1.06 (2H,
m), 0.93 (3H, t, J=7.1 Hz). Melting point (.degree. C.):
145-152.
EXAMPLE 74
(2E)-3-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-phenyl}acrylonitrile
(Compound No. 306)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.80-7.40 (3H, m),
7.35-7.15 (2H, m), 6.72 (1H, s), 6.30 (1H, d, J=6.9 Hz). Melting
point (.degree. C.): 190-192.
EXAMPLE 75
6-Chloro-3-[2-(2,2-dimethylcyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 267)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.30-7.10 (4H, m),
1.57 (1H, dd, J=8.4, 6.2 Hz), 0.91-0.85 (1H, m), 0.85 (3H, s),
0.72-0.65 (1H, m), 0.65 (3H, s). Melting point (.degree. C.):
187-188.
EXAMPLE 76
6-Chloro-3-{2-[(cis-2,
cis-3-dimethyl)-ref-1-cyclopropyl]phenoxy}-4-pyridazinol (Compound
No. 269)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.36-7.11 (4H, m),
6.68 (1H, s), 1.60 (1H, t, J=8.4 Hz), 1.09-0.93 (8H, m).
Appearance: amorphous.
EXAMPLE 77
6-Chloro-3-{2-[(cis-2,
trans-3-dimethyl)-ref-1-cyclopropyl]phenoxy}-4-pyridazinol
(Compound No. 270)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.30-7.09 (4H, m),
6.80 (1H, brs), 1.56-1.50 (1H, m), 1.10-0.95 (1H, m), 1.03 (3H, s),
0.80-0.67 (1H, m), 0.71 (3H, s). Melting point (.degree. C.):
157-160.
EXAMPLE 78
6-Chloro-3-{2-[(trans-2,
trans-3-dimethyl)-ref-1-cyclopropyl]phenoxy}-4-pyridazinol
(Compound No. 271)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.22-6.96 (4H, m),
6.70 (1H, s), 1.18-0.95 (9H, m) Melting point (.degree. C.):
181-183.
EXAMPLE 79
3-{2-[(ref-1,cis-5,cis-6)-Bicyclo[3.1.0]hex-6-yl]phenoxy}-6-chloro-4-pyrid-
azinol (Compound No. 272)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.40-7.05 (4H, m),
6.68 (1H, s), 2.05-1.60 (5H, m), 1.53 (2H, s), 1.35-1.20 (1H, m),
0.25-0.05 (1H, m). Melting point (.degree. C.): 215-240.
EXAMPLE 80
3-{2-[(ref-1,cis-5,trans-6)-Bicyclo[3.1.0]hex-6-yl]phenoxy}-6-chloro-4-pyr-
idazinol (Compound No. 273)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.20-7.10 (2H, m),
7.10-6.90 (2H, m), 6.58 (1H, s), 1.80-1.40 (8H, m), 1.20-1.00 (1H,
m). Melting point (.degree. C.): 137-139.
EXAMPLE 81
3-{2-[(ref-1,cis-6,cis-7)-Bicyclo[4.1.0]hept-7-yl]phenoxy}-6-chloro-4-pyri-
dazinol (Compound No. 274)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.44 (1H, br.d,
J=6.3 Hz), 7.35-7.10 (3H, m), 6.66 (1H, s), 2.00-1.50 (5H, m),
1.20-1.00 (4H, m), 0.90-0.65 (2H, m). Melting point (.degree. C.):
>260.
EXAMPLE 82
3-{2-[(ref-1,cis-6,trans-7)-Bicyclo[4.1.0]hept-7-yl]phenoxy}-6-chloro-4-py-
ridazinol (Compound No. 275)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.20-7.10 (2H, m),
7.05-6.85 (2H, m), 6.58 (1H, s), 1.90-1.70 (2H, m), 1.60-1.40 (3H,
m), 1.30-1.05 (6H, m). Melting point (.degree. C.): 191-193.
EXAMPLE 83
6-Chloro-3-{2-[(2,2,
cis-3-trimethyl)-ref-1-cyclopropyl]phenoxy}-4-pyridazinol (Compound
No. 279)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.30-7.00 (4H, m),
6.56 (1H, s), 1.42-1.22 (2H, m), 1.05-0.70 (9H, m). Melting point
(.degree. C.): 118-120.
EXAMPLE 84
6-Chloro-3-{2-[(2,2,
trans-3-trimethyl)-ref-1-cyclopropyl]phenoxy}-4-pyridazinol
(Compound No. 280)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.26-7.06 (4H, m),
6.59 (1H, s), 1.70-1.50 (1H, m), 1.30-1.25 (1H, m), 1.09 (3H, s),
0.96 (3H, s), 0.75 (3H, s). Melting point (C): 160-162.
EXAMPLE 85
6-Chloro-3-(2-cyclobutylphenoxy)-4-pyridazinol (Compound No.
284)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.43-7.30 (1H, m),
7.30-7.18 (2H, m), 7.08-6.98 (1H, m), 6.69 (1H, s), 3.68-3.50 (1H,
m), 2.25-1.70 (6H, m). Melting point (.degree. C.): 188-189.
EXAMPLE 86
1-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}-cyclobutanecarbonitril-
e (Compound No. 287)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.50-7.20 (5H, m),
2.70-1.80 (6H, m) Melting point (.degree. C.): 213-215.
EXAMPLE 87
1-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}-cyclobutanecarboxylica-
cid (Compound No. 288)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.42-7.35 (1H, m),
7.35-7.20 (2H, m), 7.08-7.03 (1H, m), 6.66 (1H, s), 2.80-2.45 (4H,
m), 2.22-1.95 (1H, m), 1.90-1.70 (1H, m). Melting point (.degree.
C.): 173-175.
EXAMPLE 88
6-Chloro-3-(2-cyclopentylphenoxy)-4-pyridazinol (Compound No.
292)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.41-7.35 (1H, m),
7.25-7.17 (2H, m), 7.08-7.02 (1H, m), 6.70 (1H, s), 3.14-3.06 (1H,
m), 1.98-1.52 (8H, m). Melting point (.degree. C.): 178-180.
EXAMPLE 89
6-Chloro-3-(2-cyclohexylphenoxy)-4-pyridazinol (Compound No.
293)
.sup.1H-NMR (60 MHz, CDCl.sub.3+DMF-d.sub.7) .delta. ppm: 7.40-6.70
(4H, m), 6.55 (1H s), 2.75 (1H, brs), 2.10-0.90 (10H, m). Melting
point (.degree. C.): 158-159.
EXAMPLE 90
6-Chloro-3-[2-(trifluoromethyl)phenoxy]-4-pyridazinol (Compound No.
300)
.sup.1H-NMR (90 MHz, CD30D) .delta. ppm: 7.76-7.27 (4H, m), 6.75
(1H, s), 5.47 (1H, s). Melting point (.degree. C.): 188.
EXAMPLE 91
6-Chloro-3-[2-(1-propenyl)phenoxy}-4-pyridazinol (Compound No.
305)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.70-6.90 (5H, m),
6.76 (1H, s), 6.50-6.20 (2H, m), 1.81 (3H, d, J=5.0 Hz). Melting
point (.degree. C.): 204-206.
EXAMPLE 92
3-(2-Allylphenoxy)-6-chloro-4-pyridazinol. (Compound No. 307)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.46-7.24 (4H, m),
6.96 (1H s), 6.20-5.60 (1H, m), 5.20-4.80 (2H, m), 3.46-3.26 (2H,
m). Melting point (.degree. C.): 200-202.5.
EXAMPLE 93
6-Chloro-3-[2-(1-propynyl)phenoxy]-4-pyridazinol (Compound No.
309)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.43-7.32 (2H, m),
7.23-7.16 (2H, m), 6.73 (1H, s), 1.87 (3H, s). Melting point
(.degree. C.): 182-184.
EXAMPLE 94
6-Chloro-3-[2-(cyclopropylmethyl)phenoxy]-4-pyridazinol (Compound
No. 311)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.45 (1H, dd,
J=7.3, 1.8 Hz), 7.31-7.17 (2H, m), 7.10 (1H, dd, J=7.3, 1.8 Hz),
2.38 (2H, d, J=7.0 Hz), 1.00-0.88 (1H, m), 0.50-0.40 (2H, m),
0.22-0.11 (2H, m) Melting point (.degree. C.): 165-168.
EXAMPLE 95
3-(2-Benzylphenoxy)-6-chloro-4-pyridazinol (Compound No. 315)
Melting point (.degree. C.): 185-187.
EXAMPLE 96
6-Chloro-3-[2-(methoxymethyl)phenoxy]-4-pyridazinol (Compound No.
324)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.47 (1H, br.d,
J=7.7 Hz), 7.42-7.20 (2H, m), 7.15 (1H, br.d, J=7.7 Hz), 6.83 (1H,
brs), 4.35 (2H, s), 3.23 (3H, s) Melting point (.degree. C.):
211-212.
EXAMPLE 97
6-Chloro-3-[2-(ethoxymethyl)phenoxy]-4-pyridazinol (Compound No.
325)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.47 (1H, br.d,
J=7.7 Hz), 7.42-7.20 (2H, m), 7.16 (1H, br.d, J=7.7 Hz), 6.82 (1H,
brs), 4.38 (2H, s), 3.39 (2H, q, J=7.0 Hz), 1.03 (3H, t, J=7.0 Hz).
Melting point (.degree. C.): 173-174.
EXAMPLE 98
6-Chloro-3-[2-(1,3-dioxolan-2-yl)phenoxy]-4-pyridazinol (Compound
No. 329) Melting point (.degree. C.): 143-145.
EXAMPLE 99
1-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}-ethanone
O-methyloxime (Compound No. 334)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.47 (2H, t, J=7.7
Hz), 7.31 (1H, d, J=7.7 Hz), 7.24 (1H, d, J=7.7 Hz), 6.85 (1H,
brs), 3.76 (2.8H, s), 3.58 (0.2H, s), 2.02 (2.8H, s), 1.99 (0.2H,
Melting point (.degree. C.): 165-167.
EXAMPLE 100
Methyl 2-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]-benzoate (Compound
No. 339)
.sup.1H-NMR (60 MHz, CDCl.sub.3+DMF-d.sub.7) .delta. ppm: 8.10-7.18
(4H, m), 6.80 (1H, s), 5.75 (1H, brs), 3.70 (3H, s). Melting point
(.degree. C.): 188-191.
EXAMPLE 101
3-([1,1'-Biphenyl]-2-yloxy)-6-chloro-4-pyridazinol (Compound No.
344)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.30-6.70 (10H, m),
6.25 (1H, s). Melting point (.degree. C.): 98-100.
EXAMPLE 102
6-Chloro-3-{[3'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]oxy}-4-pyridazinol
(Compound No. 348)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.65-7.58 (2H, m),
7.51-7.26 (5H, m), 7.12-7.06 (1H, m), 6.41 (1H, brs). Appearance:
paste state.
EXAMPLE 103
6-Chloro-3-{[3'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]oxy}-4-pyridazinol
(Compound No. 349)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.71-7.64 (2H, m),
7.55-7.30 (5H, m), 7.20-7.13 (1H, m), 6.43 (1H, s). Appearance:
paste state.
EXAMPLE 104
6-Chloro-3-[2-(1-pyrrolidinyl)phenoxy]-4-pyridazinol (Compound No.
355)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.19-6.73 (4H, m),
5.64 (1H, s), 3.32-3.25 (4H, m), 1.91-1.84 (4H, m). Appearance:
amorphous.
EXAMPLE 105
6-Chloro-3-[2-(1H-pyrrol-1-yl)phenoxy]-4-pyridazinol (Compound No.
356)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.41-7.27 (4H, m),
6.95-6.93 (2H, m), 6.46 (1H, m), 6.10-6.08 (2H, m). Appearance:
amorphous.
EXAMPLE 106
6-Chloro-3-[2-(2-thienyl)phenoxy]-4-pyridazinol (Compound No.
359)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.68-7.60 (1H, m),
7.45-7.05 (5H, m), 7.01-6.95 (1H, m), 6.52 (1H, s). Appearance:
amorphous.
EXAMPLE 107
6-Chloro-3-[2-(3-thienyl)phenoxy]-4-pyridazinol (Compound No.
361)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.46-7.37 (3H, m),
7.30-7.15 (4H, m). Melting point (.degree. C.): 207-209.
EXAMPLE 108
6-Chloro-3-[2-(1H-pyrazol-1-yl)phenoxy]-4-pyridazinol (Compound No.
362)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.09 (1H, d, J=2.2
Hz), 7.70 (1H, dd, J=7.5, 2.4 Hz), 7.62 (1H, d, J=2.2 Hz),
7.50-7.27 (3H, m), 6.55 (1H, s), 6.39 (1H, t, J=2.2 Hz).
Appareance: amorphous.
EXAMPLE 108
6-Chloro-3-[2-(3,5-dimethyl-1H-pyrazol-1-yl)phenoxy]-4-pyridazinol
(Compound No. 364)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.60-7.32 (4H, m),
6.52 (1H, s), 5.86 (1H, s), 2.17 (3H, s), 2.10 (3H, s). Appareance:
amorphous.
EXAMPLE 109
6-Chloro-3-{2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}-4-pyridazinol
(Compound No. 365)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.79 (1H, brs),
7.70-7.35 (5H, m), 7.06 (1H, brs), 6.68 (1H, s). Appareance:
amorphous.
EXAMPLE 111
6-Chloro-3-{2-[4-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}-4-pyridazinol
(Compound No. 366)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 8.75 (1H, s), 8.11
(1H, s), 7.80-7.74 (1H, m), 7.58-7.38 (3H, m), 6.77 (1H, s).
Appareance: oily product.
EXAMPLE 112
6-Chloro-3-{2-[5-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}-4-pyridazinol
(Compound No. 367)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 8.30 (1H, brs),
7.83-7.72 (1H, m), 7.60-7.40 (3H, m), 6.91 (1H, br.d, J=2.6 Hz),
6.78 (1H, s). Appearance: amorphous.
EXAMPLE 113
5-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}-N,N-dimethyl-1H-pyrazo-
le-1-sulfonamide(Compound No. 369)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.87 (1H, d, J=2.6
Hz), 7.78 (1H, dd, J=7.3, 1.8 Hz), 7.65-7.35 (3H, m), 7.20 (1H, s),
7.03 (1H, d, J=2.6 Hz), 2.86 (6H, s). Melting point (.degree. C.):
151-152.
EXAMPLE 114
3-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}-N,N-dimethyl-1H-pyrazo-
le-1-sulfonamide(Compound No. 368)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.19 (1H, d, J=2.9
Hz), 8.12 (1H, s), 7.97 (1H, dd, J=7.3, 2.2 Hz), 7.61 (1H, d, J=1.5
Hz), 7.50-7.33 (2H, m), 6.98 (1H, d, J=2.9 Hz), 2.83 (6H, s).
Melting point (.degree. C.): 210-212.
EXAMPLE 115
6-Chloro-3-[2-(4-methyl-1,3-thiazol-2-yl)phenoxy]-4-pyridazinol
(Compound No. 370)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.17 (1H, d, J=7.7
Hz), 7.73 (1H, d, J=7.7 Hz), 7.47 (1H, t, J=7.7 Hz), 7.28 (1H, t,
J=7.7 Hz), 7.02 (1H, s), 6.98 (1H, s), 2.56 (3H, s). Appearance:
amorphous.
EXAMPLE 116
3-[2-(1,3-Benzoxazol-2-yl)phenoxy]-6-chloro-4-pyridazinol (Compound
No. 375)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.31 (1H, dd, J=7.9,
1.6 Hz), 7.73-7.30 (7H, m), 6.78 (1H, s). Melting point (.degree.
C.): 165-167.
EXAMPLE 117
35 3-[2-(1,3-Benzothiazol-2-yl)phenoxy]-6-chloro-4-pyridazinol
(Compound No. 376)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.12 (1H, d, J=7.7
Hz), 8.00-7.84 (1H, m), 7.78 (1H, d, J=7.7 Hz), 7.62-7.05 (1H,
brs). Melting point (.degree. C.): 215-217.
EXAMPLE 118
6-Chloro-3-[2-(dimethylamino)phenoxy]-4-pyridazinol (Compound No.
379)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.17-6.96 (4H, m),
6.61 (1H, s), 2.75 (6H, s). Appareance: amorphous.
EXAMPLE 119
6-Chloro-3-(2-nitrophenoxy)-4-pyridazinol (Compound No. 383)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.16 (1H, d, J=6.0
Hz), 7.90-7.33 (3H, m), 6.78 (1H, s). Melting point (.degree. C.):
99-100.
EXAMPLE 120
6-Chloro-3-(2-ethynylphenoxy)-4-pyridazinol (Compound No. 308)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.57-7.41 (2H, m),
7.30-7.20 (2H, m), 6.71 (1H, s), 3.60 (1H, s). Melting point
(.degree. C.): 189-191.
EXAMPLE 121
6-Chloro-3-(2-methoxyphenoxy)-4-pyridazinol (Compound No. 385)
.sup.1H-NMR (60 MHz, CDCl.sub.3+DMF-d.sub.7) .delta. ppm: 7.30-6.80
(4H, m), 6.55 (1H, s), 3.69 (3H, s) Melting point (.degree. C.):
191-194.
EXAMPLE 122
6-Chloro-3-(2-ethoxyphenoxy)-4-pyridazinol (Compound No. 386)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.26-7.02 (2H, m),
6.98-6.85 (2H, m), 6.57 (1H, s), 5.35 (1H, brs), 3.92 (2H, q, J=7.0
Hz), 1.18 (t, 3H, J=7.0 Hz). Melting point (.degree. C.):
155-175.
EXAMPLE 123
6-Chloro-3-(2-isopropoxyphenoxy)-4-pyridazinol (Compound No.
387)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.28-7.10 (3H, m),
6.97 (1H, td, J=7.3, 2.3 Hz), 6.83 (1H, brs), 4.52 (1H, septet,
J=6.2 Hz), 1.07 (6H, d, J=6.2 Hz). Melting point (.degree. C.):
178-1.79.
EXAMPLE 124
6-Chloro-3-[2-(difluoromethoxy)phenoxy]-4-pyridazinol (Compound No.
390)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.40 (4H, s), 6.63
(1H, s) 6.53 (1H, t, J=73.8 Hz). Melting point (.degree. C.):
210-212.
EXAMPLE 125
6-Chloro-3-[2-(trifluoromethoxy)phenoxy]-4-pyridazinol (Compound
No. 391)
.sup.1H-NMR (200 MHz, CDCl.sub.3+CD.sub.3OD) .delta. ppm: 7.38-7.20
(4H, m), 6.60 (1H, s). Melting point (.degree. C.): 215.
EXAMPLE 126
6-Chloro-3-[2-(2-methoxyethoxy)phenoxy]-4-pyridazinol (Compound No.
396)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.26-6.93 (4H, m),
6.62 (1H, s), 4.78-4.03 (2H, m), 3.55-3.50 (2H, m), 3.24 (3H, s).
Appareance: paste state.
EXAMPLE 127
6-Chloro-3-[2-(2-hydroxyphenoxy)phenoxy]-4-pyridazinol (Compound
No. 399)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.27-6.75 (8H, m),
6.61 (1H, s). Appareance: amorphous.
EXAMPLE 128
6-Chloro-3-{2-{2-[(6-chloro-4-ethoxy-3-pyridazinyl)-oxy]phenoxy}phenoxy}-4-
-pyridazinol (Compound No. 400)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.65-6.70 (8H, m),
6.63-6.59 (2H, m), 4.19 (2H, q, J=7.0 Hz), 1.50 (3H, t, J=7.0 Hz).
Appareance: amorphous.
EXAMPLE 129
6-Chloro-3-[2-(methylsulfanyl)phenoxy]-4-pyridazinol (Compound No.
401)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.43-7.11 (4H, m),
6.71 (1H, s), 2.40 (3H, s). Melting point (.degree. C.):
174-175.
EXAMPLE 130
6-Chloro-3-[2-(isopropylsulfanyl)phenoxy]-4-pyridazinol (Compound
No. 403) Melting point (.degree. C.): 176-177.
EXAMPLE 131
6-Chloro-3-(2-cyanophenoxy)-4-pyridazinol (Compound No. 330)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.82-7.68 (2H, m),
7.46-7.34 (2H, m), 6.79 (1H, s) Appareance: amorphous.
EXAMPLE 132
1-{2-[6-Chloro-4-hydroxy-3-pyridazinyl]oxy}phenyl}-ethanone(Compound
No. 336)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.88-7.85 (1H, m),
7.65-7.57 (1H, m), 7.43-7.26 (2H, m), 6.73 (1H, s), 2.50 (3H,
br.s). Melting point (.degree. C.): 186-189.
EXAMPLE 133
6-Chloro-3-(3-chlorophenoxy)-4-pyridazinol (Compound No. 410)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.45-7.10 (5H, m),
6.72 (1H, s). Melting point (.degree. C.): 217.
EXAMPLE 134
6-Chloro-3-(3-iodophenoxy)-4-pyridazinol (Compound No. 412)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.64-7.53 (2H, m),
7.28-6.70 (3H, m). Melting point (.degree. C.): 202-203.
EXAMPLE 135
6-Chloro-3-(3-methylphenoxy)-4-pyridazinol (Compound No. 413)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.35-6.80 (4H, m),
6.95 (1H, s), 2.35 (3H, s). Melting point (.degree. C.):
205-208.
EXAMPLE 136
6-Chloro-3-(3-isopropylphenoxy)-4-pyridazinol (Compound No. 415)
Melting point (.degree. C.): 176-177.
EXAMPLE 137
3-(3-tert-Butylphenoxy)-6-chloro-4-pyridazinol (Compound No.
416)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 7.40-6.65 (4H, m),
6.67 (1H, s), 1.27 (9H, s). Melting point (.degree. C.):
203-207.
EXAMPLE 138
6-Chloro-3-(3-cyclopropylphenoxy)-4-pyridazinol (Compound No.
417)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.35-7.20 (1H, m),
6.98-6.85 (3H, m), 6.78 (1H, brs), 2.00-1.88 (1H, m), 0.98-0.87
(2H, m), 0.70-0.60 (2H, m). Melting point (.degree. C.):
179-181.
EXAMPLE 139
6-Chloro-3-[3-(trifluoromethyl)phenoxy]-4-pyridazinol (Compound No.
418)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.70-7.40 (4H, m),
6.95 (1H, s). Melting point (.degree. C.): 213-216.
EXAMPLE 140
6-Chloro-3-[3-(2-furyl)phenoxy]-4-pyridazinol (Compound No.
419)
.sup.1H-NMR (200 MHz, CDCl.sub.3+CD.sub.3OD) .delta. ppm: 7.55-7.35
(4H, m), 7.08-7.02 (1H, m), 6.67 (1H, d, J=3.3 Hz), 6.59 (1H, brs),
6.48 (1H, dd, J=3.3, 1.8 Hz). Melting point (.degree. C.):
200-202.
EXAMPLE 141
3-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]benzonitrile (Compound No.
420)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.70-7.40 (4H, m),
6.75 (1H, s). Melting point (.degree. C.): 226-229.
EXAMPLE 142
3-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]benzaldehyde (Compound No.
421)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 9.96 (1H, s),
7.72-7.53 (3H, m), 7.46-7.41 (1H, m), 6.54 (1H, s). Melting point
(.degree. C.): 188-192.
EXAMPLE 143
1-{3-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}-ethanone(Compound
No. 422)
Melting point (.degree. C.): 195-198.
EXAMPLE 144
Methyl 3-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]-benzoate (Compound
No. 423)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 8.00-7.70 (2H, m),
7.70-7.30 (2H, m), 6.75 (1H, s), 3.30 (3H, s). Melting point
(.degree. C.): 207.
EXAMPLE 145
6-Chloro-3-(3-nitrophenoxy)-4-pyridazinol (Compound No. 424)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 8.30-7.90 (2H, m),
7.90-7.70 (2H, m), 6.50 (1H, s), 5.80-5.15 (1H, brs). Melting point
(.degree. C.): 217-219.
EXAMPLE 146
6-Chloro-3-(3-methoxyphenoxy)-4-pyridazinol (Compound No. 425)
.sup.1H-NMR (60 MHz, CDCl.sub.3+DMF-d.sub.7) .delta. ppm: 7.50-7.10
(1H, m), 6.90-6.60 (3H, m), 6.70 (1H, s), 5.88 (1H, brs),
3.77Melting point (.degree. C.): 199-203.
EXAMPLE 147
6-Chloro-3-(4-chlorophenoxy)-4-pyridazinol (Compound No. 427).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.45-7.38 (2H, m),
7.23-7.15 (2H, m), 6.70 (1H, s). Melting point (.degree. C.):
226-231.
EXAMPLE 148
6-Chloro-3-(4-methylphenoxy)-4-pyridazinol (Compound No. 430)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 7.25-6.83 (4H, m),
6.68 (1H, s), 2.25. (3H, s). Melting point (.degree. C.):
261-263.
EXAMPLE 149
6-Chloro-3-(4-isopropylphenoxy)-4-pyridazinol (Compound No.
432)
Melting point (.degree. C.): 233-235.
EXAMPLE 150
3-(4-tert-Butylphenoxy)-6-chloro-4-pyridazinol (Compound No.
433)
Melting point (.degree. C.): 224-225.
EXAMPLE 151
6-Chloro-3-(4-cyclopropylphenoxy)-4-pyridazinol (Compound No.
434)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.15-7.02 (4H, m),
6.82 (1H, brs), 2.01-1.90 (1H, m), 0.99-0.90 (2H, m), 0.70-0.62
(2H, m) Melting point (.degree. C.): 221-227.
EXAMPLE 152
6-Chloro-3-(4-methoxyphenoxy)-4-pyridazinol (Compound No. 435)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.26-6.85 (4H, m),
6.80 (1H, brs), 3.81 (3H, s). Melting point (.degree. C.):
260-263.5.
EXAMPLE 153
6-Chloro-3-[4-(trimethylsilyl)phenoxy]-4-pyridazinol (Compound No.
436)
Melting point (.degree. C.): 197-199.
EXAMPLE 154
6-Chloro-3-(2,3-difluorophenoxy)-4-pyridazinol (Compound No.
437)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.24-7.05 (3H, m),
6.73 (1H, s). Melting point. (C): 188-193.
EXAMPLE 155
6-Chloro-3-(3-chloro-2-fluorophenoxy)-4-pyridazinol (Compound No.
438)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.43-7.21 (3H, m),
6.75 (1H, s). Melting point (.degree. C.): 187-195.
EXAMPLE 156
6-Chloro-3-[2-fluoro-3-(trifluoromethyl)phenoxy]-4-pyridazinol
(Compound No. 441)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.78-7.66 (2H, m),
7.48 (1H, t, J=8.1 Hz), 6.83 (1H, s). Melting point (.degree. C.):
185-189.
EXAMPLE 157
6-Chloro-3-(2,3-dichlorophenoxy)-4-pyridazinol (Compound No.
443)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.62-7.57 (1H, m),
7.50-7.37 (2H, m), 6.89 (1H, s). Melting point (.degree. C.):
233-238.
EXAMPLE 158
6-Chloro-3-[2-chloro-3-(trifluoromethyl)phenoxy]-4-pyridazinol
(Compound No. 446)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.74-7.55 (3H, m),
6.76 (1H, s). Melting point (.degree. C.): 170-200.
EXAMPLE 159
3-(2-Bromo-3-methylphenoxy)-6-chloro-4-pyridazinol (Compound No.
450)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.35 (1H, t, J=7.5
Hz), 7.27 (1H, dd, J=7.5, 2.2 Hz), 7.16 (1H, dd, J=7.5, 2.2 Hz),
6.87 (1H, brs), 2.41 (3H, s). Melting point (.degree. C.):
140-141.
EXAMPLE 160
6-Chloro-3-(3-fluoro-2-methylphenoxy)-4-pyridazinol (Compound No.
453)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.30-7.15 (1H, m),
7.08-6.85 (2H, m), 6.73 (1H, s), 2.09 (3H, d, J=1.8 Hz). Melting
point (.degree. C.): 242-244.
EXAMPLE 161
6-Chloro-3-(3-chloro-2-methylphenoxy)-4-pyridazinol (Compound No.
454)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.39-7.12 (4H, m),
2.14 (3H, s). Melting point (.degree. C.): 250-252.
EXAMPLE 162
6-Chloro-3-(2,3-dimethylphenoxy)-4-pyridazinol (Compound No.
456)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 7.22-6.98 (3H, m),
6.77 (1H, s), 2.30 (3H, s), 2.02 (3H, s). Melting point (.degree.
C.): 240-241.
EXAMPLE 163
6-Chloro-3-(2-methyl-3-nitrophenoxy)-4-pyridazinol (Compound No.
458)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.89-7.84 (1H, m),
7.58-7.47 (2H, m), 6.90 (1H, brs), 2.25 (3H, s). Melting point
(.degree. C.): 241-244.
EXAMPLE 164
6-Chloro-3-(3-methoxy-2-methylphenoxy)-4-pyridazinol (Compound No.
459)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.14 (1H, t, J=8.4
Hz), 6.78 (1H, d, J=8.4 Hz), 6.63 (1H, d, J=8.4 Hz), 6.55 (1H, s),
3.83 (3H, s), 2.00 (3H, s). Melting point (.degree. C.):
224-237.
EXAMPLE 165
6-Chloro-3-{3-[(6-chloro-4-hydroxy-3-pyridazinyl)-oxy]-2-methylphenoxy}-4--
pyridazinol (Compound No. 460)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.16 (1H, t, J=8.4
Hz), 6.85 (2H, d, J=8.4 Hz), 6.48 (2H, s), 2.15 (3H, s). Melting
point (.degree. C.): >290.
EXAMPLE 166
6-Chloro-3-(2-cyclopropyl-3-methylphenoxy)-4-pyridazinol (Compound
No. 472)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.18 (1H, t, J=7.7
Hz), 7.07 -(1H, br.d, J=7.7 Hz), 6.91 (1H, br.d, J=7.7 Hz), 6.82
(1H, brs), 2.40 (3H, s), 1.43-1.28 (1H, m), 0.79-0.68 (2H, m),
0.59-0.48 (2H, m). Melting point (.degree. C.): 197-198.
EXAMPLE 167
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
tetrahydro-2H-pyran-4-carboxylate (Compound No. 3856)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.38 (1H, s),
7.15-7.04 (2H, m), 6.90-6.78 (1H, m), 4.10-3.95 (2H, m), 3.60-3.43
(2H, m), 3.03-2.86 (1H, m), 2.11 (3H, s), 2.06-1.90 (4H, m),
1.80-1.60 (1H, m), 0.80-0.50 (4H, m). Appareance: caramel-like.
EXAMPLE 168
Methyl 2-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]-6-fluorobenzoate
(Compound No. 491)
.sup.1H-NMR (270 MHz, CDCl.sub.3) .delta. ppm: 7.62 (1H, td, J=8.4,
5.6 Hz), 7.23 (1H, t, J=8.4 Hz), 7.02 (1H, d, J=8.4 Hz), 3.83 (3H,
s). Appareance: amorphous.
EXAMPLE 169
6-Chloro-3-(3-methyl-2-nitrophenoxy)-4-pyridazinol (Compound No.
498)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.48 (1H, t, J=8.1
Hz), 7.26 (1H, d, J=8.1 Hz), 7.19 (1H, d, J=8.1 Hz), 6.66 (1H, s),
2.37 (3H, s). Melting point (.degree. C.): 191-200.
EXAMPLE 170
6-Chloro-3-(2,3-dimethoxyphenoxy)-4-pyridazinol (Compound No.
503)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.14-6.78 (4H, m),
3.84 (3H, s), 3.61 (3H, s). Melting point (.degree. C.):
199-201.
EXAMPLE 171
6-Chloro-3-(2,3-dihydro-1H-inden-4-yloxy)-4-pyridazinol (Compound
No. 506)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.20 (1H, t, J=7.3
Hz), 7.14 (1H, d, J=7.3 Hz), 6.92 (1H, d, J=7.3 Hz), 6.83 (1H,
brs), 2.92 (1H, t, J=7.3 Hz), 2.64 (1H, t, J=7.3 Hz), 2.00 (1H,
quintet, J=7.3 Hz). Melting point (.degree. C.): 230-232.
EXAMPLE 172
6-Chloro-3-[(3-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-4-pyridazinol
(Compound No. 507)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.17 (1H, t, J=7.7
Hz), 7.08 (1H, d, J=7.7 Hz), 6.88 (1H, d, J=7.7 Hz), 6.69 (1H, s),
3.35-3.15 (1H, m), 3.10-2.70 (2H, m), 2.40-2.15 (1H, m), 1.80-1.55
(1H, m), 1.15 (3H, d, J=7.0 Hz). Melting point (.degree. C.):
232.
EXAMPLE 173
6-Chloro-3-[(1-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-4-pyridazinol
(Compound No. 510)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.21 (1H, dd, J=8.1,
7.3 Hz) 7.09 (1H, d, J=7.3 Hz), 6.91 (1H, d, J=8.1 Hz), 6.70 (1H,
s), 3.30-3.05 (1H, m), 2.85-2.50 (2H, m), 2.40-2.20 (1H, m),
1.70-1.45 (1H, m), 1.29 (3H, d, J=7.0 Hz). Melting point (.degree.
C.): 228-230.
EXAMPLE 174
6-Chloro-3-[(2,2-dimethyl-2,3-dihydro-1H-inden-4-yl)oxy]-4-pyridazinol
(Compound No. 513)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.17 (1H, t, J=7.7
Hz), 7.05 (1H, d, J=7.7 Hz), 6.89 (1H, d, J=7.7 Hz), 6.69 (1H, s),
2.76 (2H, s), 2.53 (2H, s), 1.13 (6H, s). Melting point (.degree.
C.): 220-223.
EXAMPLE 175
6-Chloro-3-{spiro[cyclopropane-1,3'-(2',3'-dihydro-1'H-inden)]-4'-yloxy}-4-
-pyridazinol (Compound No. 514)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.15-6.95 (2H, m),
6.75 (1H, dd, J=6.6, 2.6 Hz), 6.66 (1H, s), 3.02 (2H, dd, J=7.7,
7.3 Hz), 2.15-1.95 (2H, m), 1.28-1.15 (2H, m), 0.80-0.70 (2H, m)
Appareance: amorphous.
EXAMPLE 176
6-Chloro-3-(4-fluorophenoxy)-4-pyridazinol (Compound No. 426)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.26-7.05 (4H, m),
6.70 (1H, s). Melting point (.degree. C.): 241-248.
EXAMPLE 177
3-(Bicyclo[4.2.0]octa-1,3,5-trien-2-yloxy)-6-chloro-4-pyridazinol
(Compound No. 505)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.22 (1H, dd, J=8.2,
7.3 Hz), 6.96 (1H, d, J=8.2 Hz), 6.91 (1H, d, J=7.3 Hz), 6.69 (1H,
s), 3.19-3.11 (2H, m), 3.10-3.00 (2H, m). Melting point (.degree.
C.): 145-155.
EXAMPLE 178
7-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-2,3-dihydro-1H-inden-1-one
0-methyloxime (Compound No. 520)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.50-7.15 (2H, m),
7.07 (1H, dd, J=8.1, 7.3 Hz), 6.55 (0.4H, s), 5.77 (0.6H, s), 3.73
(1.8H, s), 3.67 (1.2H, s), 3.15-3.00 (2H, m), 2.90-2.73 (2H, m).
Melting point (.degree. C.): >250.
EXAMPLE 179
6-Chloro-3-(5,6,7,8-tetrahydro-1-naphthalenyloxy)-4-pyridazinol
(Compound No. 521)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.14 (1H, t, J=7.7
Hz), 6.98 (1H, d, J=7.7 Hz), 6.89 (1H, d, J=7.7 Hz), 6.82 (1H,
brs), 2.80-2.70 (2H, m), 2.50-2.40 (2H, m), 1.85-1.70 (4H, m).
Melting point. (C): 232-237.
EXAMPLE 180
6-Chloro-3-(1-naphthyloxy)-4-pyridazinol (Compound No. 527)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 8.10-7.20 (7H, m),
6.85 (1H, s), 6.20 (1H, brs). Melting point (.degree. C.):
243-245.
EXAMPLE 181
6-Chloro-3-(2,3-dihydro-1-benzofuran-4-yloxy)-4-pyridazinol
(Compound No. 528)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.11 (1H, t, J=8.1
Hz), 6.65 (1H, s), 6.60 (1H, d, J=8.1 Hz), 6.56 (1H d, J=8.1 Hz),
4.53 (2H, t, J=8.5 Hz), 2.97 (2H, t, J=8.5 Hz). Melting point
(.degree. C.): 219-221.
EXAMPLE 182
6-Chloro-3-[(3-methyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-4-pyridazinol
(Compound No. 529)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.15 (1H, t, J=8.1
Hz), 6.85 (1H, brs), 6.67 (1H, d, J=8.1 Hz), 6.62 (1H, d, J=8.1
Hz), 4.65 (1H, t, J=8.8 Hz), 4.12-4.04 (1H, m), 3.50-3.39 (1H, m),
1.14 (3H, d, J=7.0 Hz). Melting point (.degree. C.): 238-245.
EXAMPLE 183
3-(1-benzofuran-4-yloxy)-6-chloro-4-pyridazinol (Compound No.
531)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.99 (1H, d, J=2.0
Hz), 7.52 20 (1H, d, J=7.8 Hz), 7.35 (1H, t, J=7.8 Hz), 7.06 (1H,
d, J=7.8 Hz), 6.87 (1H, s), 6.81 (1H, d, J=2.0 Hz). Melting point
(.degree. C.): 220-225.
EXAMPLE 184
6-Chloro-3-[(3-methyl-1-benzofuran-4-yl)oxy]-4-pyridazinol
(Compound No. 532)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.44 (1H, d, J=1.5
Hz), 7.33-7.20 (2H, m), 6.91 (1H, dd, J=7.0, 1.5 Hz), 6.61 (1H, s),
2.01 (3H, s). Melting point (.degree. C.): 218-225.
EXAMPLE 185
3-(1-Benzothien-4-yloxy)-6-chloro-4-pyridazinol (Compound No.
534)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.75 (1H, d, J=8.1
Hz), 7.53 (1H, d, J=5.5 Hz), 7.35 (1H, dd, J=8.1, 7.7 Hz), 7.28
(1H, 35 dd, J=5.5, 0.7 Hz), 7.10 (1H, dd, J=7.7, 0.7 Hz), 6.64 (1H,
s). Melting point (.degree. C.): 181-183.
EXAMPLE 186
6-Chloro-3-(8-quinolynyloxy)-4-pyridazinol (Compound No. 535)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 8.80 (1H, dd,
J=4.0, 1.5 Hz), 8.46 (1H, dd, J=8.4, 1.5 Hz), 7.93-7.87 (1H, m),
7.70-7.63 (2H, m), 7.57 (1H, dd, J=8.4, 4.0 Hz), 6.82 (1H, s).
Melting point (.degree. C.): >200 (dec.).
EXAMPLE 187
6-Chloro-3-(8-quinolynyloxy)-4-pyridazinol (Compound No. 536)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 8.81 (1H, dd,
J=4.0, 1.5 Hz), 8.41 (1H, dd, J=8.4, 1.5 Hz), 7.81 (1H, d, J=7.0
Hz), 7.62-7.52 (2H, m), 7.41 (1H, d, J=7.7 Hz), 6.43 (1H, s).
Melting point (.degree. C.): >180 (dec.).
EXAMPLE 188
6-Chloro-3-[(2-methyl-1,3-benzoxazol-4-yl)oxy]-4-pyridazinol
(Compound No. 538)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.55-7.32 (2H, m),
7.22-7.10 (1H, m), 6.73 (1H, s), 2.59 (3H, s). Melting point
(.degree. C.): 221-222.
EXAMPLE 189
6-Chloro-3-(2,3-dihydro-1-benzofuran-7-yloxy)-4-pyridazinol
(Compound No. 539)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.13-7.08 (1H, m),
6.95 (1H, d, J=7.3 Hz), 6.85 (1H, dd, J=8.1, 7.3 Hz), 6.67 (1H, s),
4.54 (2H, t, J=8.4 Hz), 3.30-3.20 (2H, m). Appareance:
amorphous.
EXAMPLE 190
6-Chloro-3-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]-4-pyridazinol
(Compound No. 540)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.08 (1H, d, J=7.3
Hz), 6.96 (1H, d, J=8.1 Hz), 6.87-6.79 (2H, m), 3.06 (2H, s), 1.37
(6H, s). Melting point (.degree. C.): 228-229.5.
EXAMPLE 191
3-(1-Benzofuran-7-yloxy)-6-chloro-4-pyridazinol (Compound No.
541)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.73 (1H, d, J=2.2
Hz), 7.53 (1H, dd, J=7.7, 1.4 Hz), 7.26 (1H, t, J=7.7 Hz), 7.15
(1H, dd, J=7.7, 1.4 Hz), 6.90 (1H, d, J=2.2 Hz), 6.76 (1H, s).
Melting point (.degree. C.): 201-202.
EXAMPLE 192
3-(1,3-Benzodioxol-4-yloxy)-6-chloro-4-pyridazinol (Compound No.
544)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 6.94-6.75 (4H, m),
6.01 (2H, s). Melting point (.degree. C.): 206-211.
EXAMPLE 193
6-Chloro-3-(2,3-dihydro-1,4-benzodioxyn-5-yloxy)-4-pyridazinol
(Compound No. 547)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 6.90-6.72 (4H, m),
4.27-4.15 (4H, m). Melting point (.degree. C.): 218-223.5.
EXAMPLE 194
6-Chloro-3-[(2-methyl-1,3-benzoxazol-7-yl)oxy]-4-pyridazinol
(Compound No. 549)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.52 (1H, dd, J=8.1,
1.1 Hz) 7.37 (1H, t, J=8.1 Hz), 7.21 (1H, dd, J=8.1, 1.1 Hz), 6.76
(1H, s), 2.65 (3H, s). Melting point (.degree. C.): 197-202.
EXAMPLE 195
6-Chloro-3-(2,4-dichlorophenoxy)-4-pyridazinol (Compound No.
552)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.55 (1H, t, J=1.8
Hz), 7.35 (2H, d, J=1.8 Hz), 6.88 (1H, s). Melting point (.degree.
C.): 233-237.
EXAMPLE 196
3-(2-Bromo-4-tert-butylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 556)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 7.61 (1H, d, J=2.0
Hz), 7.43 (1H, dd, J=8.4, 2.0 Hz), 7.17 (1H, d, J=8.4 Hz), 6.73
(1H, s), 1.32 (9H, s). Melting point (.degree. C.): >202
(dec.).
EXAMPLE 197
6-Chloro-3-(4-chloro-2-methylphenoxy)-4-pyridazinol (Compound No.
558)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6+CDCl.sub.3) .delta. ppm:
7.40-7.10 (3H, m), 6.65 (1H, s), 2.18 (3H, s). Melting point
(.degree. C.): 235-235.5.
EXAMPLE 198
6-Chloro-3-(2,4-dimethylphenoxy)-4-pyridazinol (Compound No.
559)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.17-6.98 (3H, m),
6.85 (1H, s), 2.29 (3H, s), 2.07 (3H, s). Melting point (.degree.
C.): 217.5.
EXAMPLE 199
6-Chloro-3-(2-ethyl-4-iodophenoxy)-4-pyridazinol (Compound No.
562)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.59 (1H, d, J=2.2
Hz), 7.49 (1H, dd, J=8.4, 2.2 Hz), 6.75 (1H, d, J=8.4 Hz), 6.48
(1H, s), 2.65-1.95 (2H, m), 1.16 (3H, t, J=7.7 Hz). Melting point
(.degree. C.): 199-201.
EXAMPLE 200
3-(4-Bromo-2-isopropylphenoxy)-6-chloro-4-pyridazinol (Compound No.
566)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 7.44 (1H, brs),
7.37 (1H, dd, J=8.0, 2.2 Hz), 7.00 (1H, d, J=8.0 Hz), 6.73 (1H, s),
3.01 (1H, septet, J=6.8 Hz), 1.15 (6H, d, J=6.8 Hz). Melting point
(.degree. C.): 215-225.
EXAMPLE 201
3-(2-tert-Butyl-4-methylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 567)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.25 (1H, d, J=2.0
Hz), 7.05 (1H, dd, J=8.0, 2.0 Hz), 6.85 (1H, d, J=8.0 Hz), 6.70
(1H, s), 2.30 (3H, s), 1.35 (9H, s). Melting point (.degree. C.):
230-236.
EXAMPLE 202
6-Chloro-3-(2-cyclopropyl-4-methylphenoxy)-4-pyridazinol (Compound
No. 571)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.05-6.95 (1H, m),
6.96 (1H, s), 6.81 (1H, s), 6.68 (1H, m), 2.30 (3H, s), 1.90-1.75
(1H, m), 0.90-0.70 (2H, m), 0.70-0.50 (2H, m). Melting point (IC):
239.
EXAMPLE 203
6-Chloro-3-(2-chloro-5-methylphenoxy)-4-pyridazinol (Compound No.
614)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.40 (1H, d, J=8.5
Hz), 7.15 (1H, s), 7.10 (1H, d, J=8.5 Hz), 6.70 (1H, s), 2.35 (3H,
s). Melting point (.degree. C.): 170.
EXAMPLE 204
6-Chloro-3-(5-chloro-2-methylphenoxy)-4-pyridazinol (Compound No.
618)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.28 (1H, d, J=8.8
Hz), 7.21-7.15 (1H, m), 7.16 (1H, s), 6.72 (1H, s), 2.15 (3H,
Melting point (.degree. C.): 174-180.
EXAMPLE 205
6-Chloro-3-(2,5-dimethylphenoxy)-4-pyridazinol (Compound No.
621)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.16 (1H, d, J=9.0
Hz), 7.08 (1H, d, J=9.0 Hz), 6.90 (1H, s), 6.70 (1H, s), 2.30 (3H,
s) 2.10 (3H, s). Melting point (.degree. C.): 80-83.
EXAMPLE 206
6-Chloro-3-(5-isopropyl-2-methylphenoxy)-4-pyridazinol (Compound
No. 623)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.20 (1H, d, J=7.5
Hz), 7.15-6.98 (1H, m), 6.95 (1H, s), 6.70 (1H, s), 2.88 (1H, s
J=7.5 Hz), 2.10 (3H, s), 1.23 (6H, d, J=7.5 Hz). Melting point
(.degree. C.): 168-169.
EXAMPLE 207
3-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-4-methylbenzoic acid
(Compound No. 626) Melting point (.degree. C.): 238-240.
EXAMPLE 208
3-(5-Amino-2-methylphenoxy)-6-chloro-4-pyridazinol (Compound No.
627) Melting point (.degree. C.): >310.
EXAMPLE 209
6-Chloro-3-[5-(dimethylamino)-2-methylphenoxy]-4-pyridazinol
(Compound No. 628)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.08 (1H, d, J=8.4
Hz), 6.68 (1H, s), 6.61 (1H, dd, J=8.4, 2.6 Hz), 6.50 (1H, d, J=2.6
Hz), 2.88 (6H, s), 2.02 (3H, s). Melting point (.degree. C.):
181-182.
EXAMPLE 210
6-Chloro-3-(5-methoxy-2-methylphenoxy)-4-pyridazinol (Compound No.
629)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.16 (1H, d, J=8.4
Hz), 6.78-6.67 (3H, m), 3.75 (3H, s), 2.07 (3H, s). Melting point
(.degree. C.): 170-172.
EXAMPLE 211
6-Chloro-3-(2-ethyl-5-methoxyphenoxy)-4-pyridazinol (Compound No.
635)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.15 (1H, br.d,
J=8.0 Hz), 6.74 (1H, brs), 6.73 (1H, br.d, J=8.0 Hz), 6.63 (1H, s),
3.73 (3H, s), 2.46 (2H, q, J=7.0 Hz), 1.10 (3H, t, J=7.0 Hz).
Melting point (.degree. C.): 124-126.
EXAMPLE 212
6-Chloro-3-(2-isopropyl-5-methylphenoxy)-4-pyridazinol (Compound
No. 640)
.sup.1H-NMR (60 MHz, CDCl.sub.3+DMF-d.sub.7) .delta. ppm: 7.50-6.70
(3H, m), 6.58 (1H, s), 3.30-2.60 (1H, m), 2.26 (3H, s), 1.13 (6H,
d, J=6.60 Hz). Melting point (.degree. C.): 193-195.
EXAMPLE 213
6-Chloro-3-(3,5-diisopropylphenoxy)-4-pyridazinol (Compound No.
642)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 7.25 (1H, d, J=8.0
Hz), 7.11 (1H, d, J=1.8 Hz), 6.92 (1H, dd, J=8.0, 1.8 Hz), 6.73
(1H, s), 2.84 (2H, septet, J=7.0 Hz), 1.18 (6H, d, J=7.0 Hz), 1.12
(6H, d, J=7.0 Hz). Melting point (.degree. C.): 231-235.
EXAMPLE 214
3-(2-tert-Butyl-5-methylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 650)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.35 (1H, d, J=8.0
Hz), 6.95 (1H, dd, J=8.0, 1.5 Hz), 6.80 (1H, s), 6.70 (1H, s), 2.27
(3H, s), 1.35 (9H, s). Melting point (.degree. C.): 226.
EXAMPLE 215
6-Chloro-3-(2,5-di-tert-butylphenoxy)-4-pyridazinol (Compound No.
653)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.50-7.10 (3H, m),
6.94 (1H, s), 4.98 (1H brs), 1.37 (9H, s), 1.28 (9H, s). Melting
point (.degree. C.): 249-258.
EXAMPLE 216
6-Chloro-3-(2-cyclopropyl-5-fluorophenoxy)-4-pyridazinol (Compound
No. 658)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.10-6.85 (3H, m),
6.72 (1H, s), 1.92-1.75 (1H, m), 0.85-0.70 (2H, m), 0.70-0.54 (2H,
m). Melting point (.degree. C.): 227-228.
EXAMPLE 217
6-Chloro-3-(5-chloro-2-cyclopropylphenoxy)-4-pyridazinol (Compound
No. 659)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.19 (1H, d, J=7.7
Hz), 7.16 (1H, s), 7.01 (1H, d, J=7.7 Hz), 6.72 (1H, s), 1.94-1.79
(1H, m), 0.90-0.75 (2H, m), 0.75-0.58 (2H, m). Melting point
(.degree. C.): 194-195.
EXAMPLE 218
6-Chloro-3-(2-cyclopropyl-5-methylphenoxy)-4-pyridazinol (Compound
No. 662)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.96 (1H, d, J=7.7
Hz), 6.89 (1H, s), 6.87 (1H, d, J=7.7 Hz), 6.68 (1H, s), 2.28 (3H,
s), 1.87-1.73 (1H, m), 0.80-0.51 (4H, m) Melting point (.degree.
C.): 150-159.
EXAMPLE 219
6-Chloro-3-(2-cyclopropyl-5-ethylphenoxy)-4-pyridazinol (Compound
No. 663)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.01 (1H, d, J=8.0
Hz), 6.92 (1H, s), 6.92 (1H, d, J=8.0 Hz), 6.69 (1H, s), 2.61 (2H,
t, J=7.7 Hz), 1.88-1.72 (1H, m), 1.20 (3H, q, J=7.7 Hz), 0.82-0.66
(2H, m), 0.65-0.52 (2H, m). Appareance: amorphous.
EXAMPLE 220
6-Chloro-3-(2-cyclopropyl-5-isopropylphenoxy)-4-pyridazinol
(Compound No. 664)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.05 (1H, dd, J=7.7,
1.8 Hz), 7.00 (1H, brs), 6.93 (1H, d, J=7.7 Hz), 6.70 (1H, s), 2.87
(1H, septet, J=7.0 Hz), 1.90-1.72 (1H, m), 1.22 (6H, d, J=7.0 Hz),
0.85-0.68 (2H, m), 0.68-0.52 (2H, m). Melting point (.degree. C.):
211-212.
EXAMPLE 221
3-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-4-cyclopropylbenzonitrile
(Compound No. 667)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.58-7.48 (2H, m),
7.15 (1H, d, J=8.8 Hz), 6.74 (1H, s), 2.10-1.90 (1H, m), 1.05-0.93
(2H, m), 0.83-0.70 (2H, m). Melting point (.degree. C.):
211-212.
EXAMPLE 222
6-Chloro-3-[5-fluoro-2-(1-propenyl)phenoxy]-4-pyridazinol (Compound
No. 679)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.61-7.53 (1H, m),
7.03-6.90 (2H, m), 6.72 (1H, s), 6.44-6.19 (2H, m), 1.80 (3H, d,
J=5.5 Hz). Melting point (.degree. C.): 210-217.
EXAMPLE 223
6-Chloro-3-[5-chloro-2-(1-propenyl)phenoxy]-4-pyridazinol (Compound
No. 680)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.55 (1H, d, J=8.4
Hz), 7.24-7.17 (2H, m), 6.72 (1H, s), 6.46-6.30 (2H, m), 1.81 (3H,
d, J=5.1 Hz). Melting point (.degree. C.): 221-224.
EXAMPLE 224
2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-4-(dimethylamino)benzaldehyde
(Compound No. 692)
.sup.1H-NMR (90 MHz, DMSO-d.sub.6) .delta. ppm: 9.78 (1H, s), 7.69
(1H, d, J=6.0 Hz), 6.81 (1H, s), 6.78-6.46 (2H, m), 3.05 (6H, s).
Melting point (.degree. C.): 124-127.
EXAMPLE 225
3-(5-Chloro-2-methoxyphenoxy)-6-chloro-4-pyridazinol (Compound No.
701)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.23-7.18 (2H, m),
7.05 (1H, d, J=8.8 Hz), 6.66 (1H, s), 3.73 (3H, s). Melting point
(.degree. C.): 143-155.
EXAMPLE 226
3-(5-Bromo-2-methoxyphenoxy)-6-chloro-4-pyridazinol (Compound No.
702)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.39-7.31 (2H, m),
7.02 (1H, d, J=8.4 Hz), 6.67 (1H, s), 3.74 (3H, s). Melting point
(.degree. C.): 135-137.
EXAMPLE 227
6-Chloro-3-(4-fluoro-2-methylphenoxy)-4-pyridazinol (Compound No.
557)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.14-6.88 (3H, m),
6.71 (1H, s), 2.16 (3H, s). Melting point (.degree. C.):
249-250.
EXAMPLE 228
3-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-4-methoxybenzonitrile
(Compound No. 707)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.66 (1H, dd, J=8.4,
2.2 Hz), 7.58 (1H, d, J=2.2 Hz), 7.26 (1H, d, J=8.4 Hz), 6.71 (1H,
s), 3.85 (3H, s). Melting point (.degree. C.): 187-192.
EXAMPLE 229
6-Chloro-3-(2-methoxy-5-nitrophenoxy)-4-pyridazinol (Compound No.
708)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.18 (1H, dd, J=9.2,
2.6 Hz) 8.04 (1H, d, J=2.6 Hz), 7.27 (1H, d, J=9.2 Hz), 6.59 (1H,
s), 3.89 (3H, s). Appareance: amorphous.
EXAMPLE 230
6-Chloro-3-(2,5-dimethoxyphenoxy)-4-pyridazinol (Compound No.
709)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.04-6.99 (1H, m),
6.81-6.78 (2H, m), 6.68 (1H, s), 3.76 (3H, s), 3.70 (3H, s).
Melting point (.degree. C.): 150-152.
EXAMPLE 231
6-Chloro-3-(2,6-difluorophenoxy)-4-pyridazinol (Compound No.
710)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.54-7.20 (3H, m),
6.88 (1H, s). Melting point (.degree. C.): 209-213.
EXAMPLE 232
6-Chloro-3-(2-chloro-6-fluorophenoxy)-4-pyridazinol (Compound No.
711)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.35-7.13 (3H, m),
6.61 (1H, s). Melting point (.degree. C.): 235.
EXAMPLE 233
3-(2-Bromo-6-fluorophenoxy)-6-chloro-4-pyridazinol (Compound No.
712)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.31-7.15 (3H, m),
6.65 (1H, s). Appareance: amorphous.
EXAMPLE 234
6-Chloro-3-(2-fluoro-6-propylphenoxy)-4-pyridazinol (Compound No.
716) Melting point (.degree. C.): 134-137.
EXAMPLE 235
6-Chloro-3-(2-fluoro-6-isopropylphenoxy)-4-pyridazinol (Compound
No. 717)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.35-7.15 (3H, m),
6.89 (1H, brs), 3.02 (1H, septet, J=7.0 Hz), 1.14 (6H, J=7.0 Hz).
Melting point (.degree. C.): 215-220.
EXAMPLE 236
6-Chloro-3-(2-cyclopropyl-6-fluorophenoxy)-4-pyridazinol (Compound
No. 719)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.22-6.96 (2H, m),
6.81-6.71 (1H, m), 6.72 (1H, s), 2.03-1.89 (1H, m), 0.93-0.80 (2H,
m), 0.69-0.62 (2H, m). Melting point (.degree. C.): 200-203.
EXAMPLE 237
6-Chloro-3-{2-[1-(ethylsulfanyl)ethyl]-6-fluorophenoxy}-4-pyridazinol
(Compound No. 728)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.42 (1H, d, J=8.1
Hz), 7.26-7.15 (1H, m), 7.07-6.97 (1H, m), 6.46 (1H, s), 4.33 (1H,
q, J=7.0 Hz), 2.42-2.20 (2H, m), 1.43 (3H, d, J=7.0 Hz), 1.02 (3H,
t, J=7. 0 Hz) Physical property: amorphous.
EXAMPLE 238
6-Chloro-3-(2-fluoro-6-nitrophenoxy)-4-pyridazinol (Compound No.
731)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.03-7.99 (1H, m),
7.78-7.53 (2H, m), 6.89 (1H, s) Melting point (.degree. C.): 210
(sublimation).
EXAMPLE 239
6-Chloro-3-(2-fluoro-6-methoxyphenoxy)-4-pyridazinol (Compound No.
732)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.26 (1H, dd,
J=15.0, 8.1 Hz), 7.02-6.91 (2H, m), 6.84 (1H, s), 3.75 (3H, s).
Melting point (.degree. C.): 190-194 (sublimation).
EXAMPLE 240
6-Chloro-3-(2,6-dichlorophenoxy)-4-pyridazinol (Compound No.
733)
.sup.1H-NMR (90 MHz, DMSO-d.sub.6) .delta. ppm: 7.70-7.10 (3H, m),
6.80 (1H, s). Melting point (.degree. C.): 265.
EXAMPLE 241
6-Chloro-3-(2-chloro-6-iodophenoxy)-4-pyridazinol (Compound No.
735)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.90 (1H, d, J=8.1
Hz), 7.64 (1H, d, J=8.1 Hz), 7.12 (1H, t, J=8.1 Hz), 7.02-6.80 (1H,
br.m). Melting point (.degree. C.): 262-264.
EXAMPLE 242
6-Chloro-3-(2-chloro-6-methylphenoxy)-4-pyridazinol (Compound No.
736)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.50-7.00 (3H, m),
6.75 (1H, s), 2.22 (3H, s). Melting point (.degree. C.): 235.
EXAMPLE 243
6-Chloro-3-(2-chloro-6-ethylphenoxy)-4-pyridazinol (Compound No.
737)
Melting point (.degree. C.): 194-195.
EXAMPLE 244
6-Chloro-3-(5-fluoro-2-methoxyphenoxy)-4-pyridazinol (Compound No.
700)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.13-6.94 (3H, m),
6.71 (1H, s), 3.74 (1H, s). Melting point (.degree. C.):
187-191.
EXAMPLE 245
6-Chloro-3-(2-chloro-6-cyclopropylphenoxy)-4-pyridazinol (Compound
No. 740)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.30 (1H, dd, J=8.1,
1.5 Hz), 7.17 (1H, dd, J=8.1, 7.7 Hz), 6.96 (1H, dd, J=7.7, 1.5
Hz), 6.76 (1H, s), 2.00-1.84 (1H, m), 0.95-0.80 (2H, m), 0.70-0.60
(2H, m). Melting point (.degree. C.): 224-225.
EXAMPLE 246
6-Chloro-3-[2-chloro-6-(2-methyl-2-propenyl)phenoxy]-4-pyridazinol
(Compound No. 746)
Melting point (.degree. C.): 198-200.
EXAMPLE 247
6-Chloro-3-(2-chloro-6-nitrophenoxy)-4-pyridazinol (Compound No.
754)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.12 (1H, dd, J=8.1,
1.5 Hz), 7.95 (1H, dd, J=8.1, 1.5 Hz), 7.59 (1H, t, J=8.1 Hz), 6.76
(1H, s). Appearance: amorphous.
EXAMPLE 248
6-Chloro-3-(2,6-dibromophenoxy)-4-pyridazinol (Compound No.
756)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.65 (2H, d, J=8.1
Hz), 7.11 (1H, t, J=8.1 Hz), 6.74 (1H, brs). Melting point
(.degree. C.): 274-278.
EXAMPLE 249
3-(2-Bromo-6-methylphenoxy)-6-chloro-4-pyridazinol (Compound No.
758)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.56 (1H, br.d,
J=7.7 Hz) 7.36 (1H, br.d, J=7.7 Hz), 7.16 (1H, t, J=7.7 Hz), 6.92
(1H, brs), 2.14 (3H, s). Melting point (.degree. C.): 242-243.
EXAMPLE 250
3-(2-Bromo-6-ethylphenoxy)-6-chloro-4-pyridazinol (Compound No.
759)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.49 (1H, dd, J=7.9,
1.6 Hz), 7.32 (1H, dd, J=7.9, 1.6 Hz), 7.14 (1H, t, J=7.9 Hz), 6.75
(1H, s), 2.58 (2H, q, J=7.5 Hz), 1.18 (3H, t, J=7.5 Hz). Melting
point (.degree. C.): 215-217.
EXAMPLE 251
3-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-4-methoxybenzonitrile
(Compound No. 707)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.66 (1H, dd, J=8.4,
2.2 Hz), 7.58 (1H, d, J=2.2 Hz), 7.26 (1H, d, J=8.4 Hz), 6.71 (1H,
s), 3.85 (3H, s). Melting point (.degree. C.): 187-192.
EXAMPLE 252
3-(2-Bromo-6-chlorophenoxy)-6-chloro-4-pyridazinol (Compound No.
734)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.64 (1H, dd, J=1.5
Hz, 8.1 Hz), 7.52 (1H, dd, J=1.5 Hz, 8.0 Hz), 7.21 (1H, t, J=8.1
Hz), 6.76 (1H, s). Melting point (.degree. C.): 266-274.
EXAMPLE 253
3-(2-Bromo-6-cyclopropylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 762)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.51 (1H, d, J=7.8
Hz), 7.14 (1H, t, J=7.8 Hz), 7.02 (1H, d, J=7.8 Hz), 6.89 (1H, s),
1.89-1.75 (1H, m), 0.88-0.75 (2H, m), 0.75-0.58 (2H, m). Melting
point (.degree. C.): 230-232.
EXAMPLE 254
3-Bromo-2-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]-benzonitrile
(Compound No. 775)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.00 (1H, dd, J=8.1,
1.5 Hz), 7.82 (1H, dd, J=8.1, 1.5 Hz), 7.37 (1H, t, J=8.1 Hz), 6.75
(1H, s). Melting point (.degree. C.): 188 (dec.).
EXAMPLE 255
3-(2-Bromo-6-methoxyphenoxy)-6-chloro-4-pyridazinol (Compound No.
778)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.26-7.05 (3H, m),
6.70 (1H, s), 3.78 (3H, s). Melting point (.degree. C.):
220-221.
EXAMPLE 256
6-Chloro-3-(2-iodo-6-methylphenoxy)-4-pyridazinol (Compound No.
780)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.70 (1H, d, J=7.7
Hz), 7.29 (1H, d, J=8.1 Hz), 6.95 (1H, t, J=7.7 Hz), 6.76 (1H, s),
2.20 (3H, s). Melting point (.degree. C.): 250-252.
EXAMPLE 257
6-Chloro-3-(2-ethyl-6-iodophenoxy)-4-pyridazinol (Compound No.
781)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.72 (1H, dd, J=7.7,
1.5 Hz), 7.33 (1H, dd, J=7.7, 1.5 Hz), 7.00 (1H, t, J=7.7 Hz), 6.76
(1H, s), 2.57 (2H, q, J=7.7 Hz), 1.17 (3H, t, J=7.7 Hz). Melting
point (.degree. C.): 242-244.
EXAMPLE 258
6-Chloro-3-(2-iodo-6-isopropylphenoxy)-4-pyridazinol (Compound No.
782)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.70 (1H, dd, J=8.0,
1.5 Hz) 7.40 (1H, dd, J=8.0, 1.5 Hz), 7.03 (1H, t, J=8.0 Hz), 6.76
(1H, s), 3.01 (1H, septet, J=7.0 Hz), 1.18 (6H, d, J=7.0 Hz).
Melting point (.degree. C.): 250-255.
EXAMPLE 259
3-Bromo-2-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]-benzonitrile
(Compound No. 775)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.00 (1H, dd, J=8.1,
1.5 Hz), 7.82 (1H, dd, J=8.1, 1.5 Hz), 7.37 (1H, t, J=8.1 Hz), 6.75
(1H, s). Melting point (.degree. C.): 188 (dec.).
EXAMPLE 260
6-Chloro-3-(2-ethyl-6-methylphenoxy)-4-pyridazinol (Compound No.
802)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.12-6.97 (3H, m),
6.52 (1H, s), 2.37 (2H, q, J=7.6 Hz), 1.95 (3H, s), 1.04 (3H, t,
J=7.6 Hz). Appearance: amorphous.
EXAMPLE 261
6-Chloro-3-(2-isopropyl-6-methylphenoxy)-4-pyridazinol (Compound
No. 803)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.23-7.06 (3H, m),
6.72 (1H, s), 2.96 (1H, septet, J=7.0 Hz), 2.10 (3H, s), 1.16 (6H,
d, J=7.0 Hz). Melting point (.degree. C.): 215-220.
EXAMPLE 262
3-(2-s-Butyl-6-methylphenoxy)-6-chloro-4-pyridazinol (Compound No.
804)
Melting point (.degree. C.): 187-189.
EXAMPLE 263
6-Chloro-3-[2-(2,2-dichlorocyclopropyl)-6-methylphenoxy]-4-pyridazinol
(Compound No. 827)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.25 (1H, br.d,
J=6.2 Hz), 7.16 (1H, dd, J=7.7, 7.3 Hz), 6.98 (1H, br.d, J=7.7 Hz),
6.72 (1H, s), 2.85 (1H, dd, J=11.0, 10.6 Hz), 2.22 (3H, s). Melting
point (.degree. C.): 213-215.
EXAMPLE 264
6-Chloro-3-(2-methyl-6-vinylphenoxy)-4-pyridazinol (Compound No.
834)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.46 (1H, dd, J=6.6,
2.6 Hz), 7.25-7.05 (2H, m), 6.71 (1H, dd, J=17.6, 11.4 Hz), 6.70
(1H, s), 5.74 (1H, dd, J=17.6, 1.5 Hz), 5.21 (1H, dd, J=11.4, 1.5
Hz), 2.11 (3H, s). Appearance: amorphous.
EXAMPLE 265
6-Chloro-3-(6-cyclopropyl-3-fluoro-2-methylphenoxy)-4-pyridazinol
(Compound No. 1052)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.92-6.70 (3H, m),
2.06 (3H, d, J=2.2 Hz), 1.85-1.70 (1H, m), 0.79-0.45 (4H, m).
Melting point (.degree. C.): 230-231.
EXAMPLE 266
6-Chloro-3-(2-methyl-6-nitrophenoxy)-4-pyridazinol (Compound No.
844)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.95 (1H, d, J=8.1
Hz), 7.76 (1H, d, J=7.7 Hz), 7.45 (1H, dd, J=8.1, 7.7 Hz), 6.80
(1H, s), 2.20 (3H, s). Appearance: paste state.
EXAMPLE 267
6-Chloro-3-(2-methoxy-6-methylphenoxy)-4-pyridazinol (Compound No.
845)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.10-7.01 (1H, m),
6.79-6.72 (2H, m), 6.55 (1H, s), 3.64 (3H, s), 2.08 (3H, s).
Appearance: amorphous.
EXAMPLE 268
6-Chloro-3-(2,6-diethylphenoxy)-4-pyridazinol (Compound No.
846)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 10.21 (1H, brs), 7.02
(3H, brs), 6.47 (1H, s), 2.27 (4H, q, J=7.6 Hz), 0.98 (6H, t, J=7.6
Hz). Melting point (.degree. C.): 181-185.
EXAMPLE 269
6-Chloro-3-(2-cyclopropyl-6-ethylphenoxy)-4-pyridazinol (Compound
No. 850)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.11 (2H, d, J=4.8
Hz), 6.85 (1H, t, J=4.8 Hz), 6.71 (1H, s), 2.52 (2H, q, J=7.5 Hz),
1.87-1.72 (1H, m), 1.16 (3H, t, J=7.5 Hz), 0.80-0.65 (2H, m),
0.65-0.50 (2H, m). Appearance: amorphous.
EXAMPLE 270
6-Chloro-3-(2,6-dipropylphenoxy)-4-pyridazinol (Compound No.
890)
Melting point (.degree. C.): 191-193.
EXAMPLE 271
6-Chloro-3-(2,6-diisopropylphenoxy)-4-pyridazinol (Compound No.
894)
.sup.1H-NMR (90 MHz, DMSO-d.sub.6) .delta. ppm: 7.28 (3H, s), 6.80
(1H, s), 2.88 (2H, septet, J=7.0 Hz), 1.15 (12H, d, J=7.0 Hz).
Melting point (.degree. C.): >285.
EXAMPLE 272
6-Chloro-3-(2-cyclopropyl-6-isopropylphenoxy)-4-pyridazinol
(Compound No. 896)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.22-7.12 (2H, m),
6.83 (1H, brs), 6.82 (1H, dd, J=6.6, 2.2 Hz), 2.91 (1H, septet,
J=7.0 Hz), 1.74-1.63 (1H, m), 1.11 (6H, d, J=7.0 Hz), 0.75-0.71
(2H, m), 0.58-0.50 (2H, m). Melting point (.degree. C.):
242-245.
EXAMPLE 273
6-Chloro-3-(2-isopropyl-6-nitrophenoxy)-4-pyridazinol (Compound No.
911)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 8.00 (1H, d, J=7.7
Hz), 7.88 (1H, d, J=7.7 Hz), 7.54 (1H, t, J=7.7 Hz), 6.96 (1H,
brs), 3.07 (1H, septet, J=7.0 Hz), 1.16 (6H, d, J=7.0 Hz). Melting
point (.degree. C.): 205-209.
EXAMPLE 274
3-(2-tert-Butyl-6-cyclopropylphenoxy)-6-chloro-4-pyridazinol
(Compound No. 914)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.28 (1H, br.d,
J=8.1 Hz), 7.10 (1H, dd, J=8.1 and 7.7 Hz), 6.90 (1H, d, J=7.7 Hz),
6.70 (1H, s), 1.80-1.55 (1H, m), 1.34 (9H, s), 0.85-0.60 (2H, m),
0.50-0.20 (2H, m) Melting point (.degree. C.): 230-231.
EXAMPLE 275
6-Chloro-3-(2,6-dicyclopropylphenoxy)-4-pyridazinol (Compound No.
931)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.08 (1H, t, J=7.7
Hz), 6.81 (2H, d, J=7.7 Hz), 6.71 (1H, s), 1.95-1.75 (2H, m),
0.85-0.70 (4H, m), 0.70-0.50 (4H, m). Melting point (.degree. C.):
232-234.
EXAMPLE 276
6-Chloro-3-(2-cyclopropyl-6-methoxyphenoxy)-4-pyridazinol (Compound
No. 964)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.13 (1H, t, J=8.1
Hz), 6.92 (1H, d, J=8.1 Hz), 6.81 (1H, brs), 6.54 (1H, d, J=8.1
Hz), 3.68 (3H, s), 1.87-1.78 (1H, m), 0.87-0.78 (2H, m), 0.64-0.56
(2H, m). Melting point (.degree. C.): 194-199.
EXAMPLE 277
6-Chloro-3-(2-cyclopropyl-6-ethoxyphenoxy)-4-pyridazinol (Compound
No. 965)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.07 (1H, t, J=8.1
Hz), 6.84 (1H, dd, J=8.4, 1.5 Hz), 6.71 (1H, s), 6.54 (1H, dd,
J=8.4, 1.5 Hz), 3.97 (2H, q, J=7.0 Hz), 2.04-1.91 (1H, m), 1.18
(3H, t, J=7.0 Hz), 0.89-0.79 (2H, m), 0.66-0.60 (2H, m). Melting
point (.degree. C.): 174-179.
EXAMPLE 278
6-Chloro-3-{2,6-di[(1E)-1-propenyl]phenoxy}-4-pyridazinol (Compound
No. 979)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.40 (2H, d, J=7.8
Hz), 7.15 (1H, t, J=7.8 Hz), 6.72 (1H, s), 6.34 (2H, d, J=16.4 Hz),
6.27 (2H, dd, J=16.4, 4.9 Hz), 1.79 (6H, d, J=4.9 Hz) Melting point
(.degree. C.): 163-164.
EXAMPLE 279
6-Chloro-3-(2,6-diallylphenoxy)-4-pyridazinol (Compound No.
982)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.20-7.15 (3H, m),
6.70 (1H, s), 5.95-5.75 (2H, m), 5.02-4.87 (4H, m), 3.26 (4H, d,
J=6.8 Hz). Melting point (.degree. C.): 131-135.
EXAMPLE 280
6-Chloro-3-(2,6-dimethoxyphenoxy)-4-pyridazinol (Compound No.
987)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.19 (1H t, J=8.3
Hz), 6.79-6.75 (3H m), 3.71 (6H, s). Melting point (.degree. C.):
199-201.
EXAMPLE 281
6-Chloro-3-(3,5-dimethylphenoxy)-4-pyridazinol (Compound No.
998)
.sup.1H-NMR (60 MHz, DMSO-d.sub.6) .delta. ppm: 6.90-6.65 (4H, m),
2.27 (6H, s). Melting point (.degree. C.): 178-182.
EXAMPLE 282
6-Chloro-3-(3-isopropyl-5-methylphenoxy)-4-pyridazinol (Compound
No. 1000)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.94 (1H, s), 6.84
(1H, s) 6.81 (1H, s), 6.69 (1H, s), 2.87 (1H, septet, J=7.0 Hz),
2.32 (3H, s), 1.23 (6H, d, J=7.0 Hz). Melting point (.degree. C.):
204-206.
EXAMPLE 283
6-Chloro-3-(3,5-diisopropylphenoxy)-4-pyridazinol (Compound No.
1007)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.98 (1H, s), 6.87
(1H, s) 6.86 (1H, s), 6.68 (1H, s), 2.90 (2H, septet, J=7.0 Hz),
1.24 (12H, d, J=7.0 Hz). Melting point (.degree. C.): 249-253.
EXAMPLE 284
3-[3,5-Bis(trifluoromethyl)phenoxy]-6-chloro-4-pyridazinol
(Compound No. 1009)
.sup.1H-NMR (200 MHz, DMF-d.sub.7) .delta. ppm: 8.20-7.80 (3H, m),
6.94 (1H, s), 5.50-4.50 (1H, brs). Melting point (.degree. C.):
237-242.
EXAMPLE 285
3-(2-Bromo-3,5-dimethylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 1013)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.11 (1H, s), 7.00
(1H, s), 6.86 (1H, brs), 2.37 (3H, s), 2.27 (3H, s). Melting point
(.degree. C.): 240-244.
EXAMPLE 286
6-Chloro-3-(2,3,5-trimethylphenoxy)-4-pyridazinol (Compound No.
1016)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 6.90 (1H, s), 6.75
(1H, s) 6.70 (1H, s), 2.30 (6H, s), 2.02 (3H, s). Melting point
(.degree. C.): 223-224.
EXAMPLE 287
6-Chloro-3-(3,5-dimethyl-2-propylphenoxy)-4-pyridazinol (Compound
No. 1020)
.sup.1H-NMR (90 MHz, DMSO-d.sub.6) .delta. ppm: 6.90 (1H, s), 6.81
(1H, s), 6.77 (1H, s), 2.29 (3H, s), 2.21 (3H, s), 2.53-2.19 (2H,
m), 1.57-1.29 (2H, m), 0.86 (3H, t, J=6.6 Hz). Melting point
(.degree. C.): 154.5.
EXAMPLE 288
6-Chloro-3-(2-cyclopropyl-3,5-dimethylphenoxy)-4-pyridazinol
(Compound No. 1023)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.89 (1H, s), 6.73
(1H, s) 6.69 (1H, s), 2.39 (3H, s), 2.26 (3H, s), 1.45-1.28 (1H,
m), 0.78-0.67 (2H, m), 0.65-0.51 (2H, m). Melting point (.degree.
C.): 200-203.
EXAMPLE 289
6-Chloro-3-[3,5-dimethyl-2-(methylsulfanyl)phenoxy]-4-pyridazinol
(Compound No. 1027)
Melting point (.degree. C.): 213-214.
EXAMPLE 290
3-(2-Bromo-3,6-dimethylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 1040)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.16 (1H, d, J=7.9
Hz), 7.10 (1H, d, J=7.9 Hz), 6.72 (1H, s), 2.38 (3H, s), 2.16 (3H,
s). Melting point (.degree. C.): 255-257.
EXAMPLE 291
3-(6-Bromo-3-fluoro-2-methylphenoxy)-6-chloro-4-pyridazinol
(Compound No. 1050)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.51 (1H, dd, J=8.8,
5.9 Hz), 7.00 (1H, t, J=8.8 Hz), 6.96 (1H, s), 2.13 (3H, d, J=2.2
Hz). Appearance: amorphous.
EXAMPLE 292
3-(6-Bromo-3-chloro-2-methylphenoxy)-6-chloro-4-pyridazinol
(Compound No. 1053)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.47 (1H, d, J=8.1
Hz), 7.23 (1H, d, J=8.1 Hz), 6.64 (1H, s), 2.24 (3H, s). Melting
point (.degree. C.): 254-260.
EXAMPLE 293
6-Chloro-3-(3-chloro-6-cyclopropyl-2-methylphenoxy)-4-pyridazinol
(Compound No. 1055)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.18 (1H, d, J=8.4
Hz), 6.81 (1H, d, J=8.4 Hz), 6.64 (1H, s), 2.17 (3H, s), 1.89-1.76
(1H, m), 0.80-0.71 (2H, m), 0.68-0.51 (2H, m). Melting point
(.degree. C.): 233.
EXAMPLE 294
3-(6-Bromo-2,3-dimethylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 1058)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.34 (1H, d, J=8.1
Hz), 6.99 (1H, d, J=8.1 Hz), 6.71 (1H, s), 2.28 (3H, s), 2.12 (3H,
s). Melting point (.degree. C.): 263-268.
EXAMPLE 295
6-Chloro-3-(2,3,6-trimethylphenoxy)-4-pyridazinol (Compound No.
1060)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.0 (2H, s), 6.73
(1H, s), 2.27 (3H, s), 2.07 (3H, s), 2.03 (3H, s). Melting point
(.degree. C.): 228.
EXAMPLE 296
6-Chloro-3-(6-cyclopropyl-2,3-dimethylphenoxy)-4-pyridazinol
(Compound No. 1061)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.96 (1H, d, J=8.1
Hz), 6.72 (1H, d, J=8.1 Hz), 6.69 (1H, s), 2.24 (3H, s), 2.04 (3H,
s), 1.85-1.70 (1H, m), 0.75-0.46 (4H, m). Melting point (.degree.
C.): 229-234.
EXAMPLE 297
2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-3,4-dimethylbenzaldehyde
0-methyloxime (Compound No. 1063)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.98 (1H, s), 7.50
(1H, d, J=8.1 Hz), 7.11 (1H, d, J=8.1 Hz), 6.69 (1H, s), 3.81 (3H,
s), 2.32 (3H, s), 2.06 (3H, s). Appearance: amorphous.
EXAMPLE 298
6-Chloro-3-(6-methoxy-2,3-dimethylphenoxy)-4-pyridazinol (Compound
No. 1064)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.00 (1H, d, J=8.4
Hz), 6.78 (1H, d, J=8.4 Hz), 6.66 (1H, s), 3.69 (3H, s), 2.23 (3H,
s), 2.08 (3H, s). Appearance: amorphous.
EXAMPLE 299
3-(6-Bromo-3-methoxy-2-methylphenoxy)-6-chloro-4-pyridazinol
(Compound No. 1066)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.42 (1H, d, J=9.2
Hz), 6.82 (1H, d, J=9.2 Hz), 6.69 (1H, s), 3.86 (3H, s), 2.05 (3H,
s). Melting point (.degree. C.): 246-253.
EXAMPLE 300
6-Chloro-3-(6-cyclopropyl-3-methoxy-2-methylphenoxy)-4-pyridazinol
(Compound No. 1069)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.83 (1H, d, J=8.8
Hz), 6.75 (1H, d, J=8.8 Hz), 6.66 (1H, s), 3.81 (3H, s), 1.99 (3H,
s), 1.78-1.70 (1H, m), 0.69-0.63 (2H, m), 0.52-0.47 (2H, m).
Melting point (.degree. C.): 250-253.
EXAMPLE 301
6-Chloro-3-(2-cyclopropyl-3,6-dimethylphenoxy)-4-pyridazinol
(Compound No. 1073)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.20 (1H, d, J=7.6
Hz), 6.95 (1H, d, J=7.6 Hz), 6.68 (1H, s), 2.39 (3H, s), 2.10 (3H,
s), 1.50-1.25 (1H, m), 0.90-0.70 (2H, m), 0.70-0.50 (2H, m).
Melting point (.degree. C.): 171-175.
EXAMPLE 302
3-(2-Allyl-6-ethyl-3-methoxyphenoxy)-6-chloro-4-pyridazinol
(Compound No. 1080)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.11 (1H, d, J=8.4
Hz), 6.85 (1H, s), 6.83 (1H, d, J=8.4 Hz), 6.10-5.30 (1H, m),
5.00-4.60 (2H, m), 3.83 (3H, s), 3.30-3.10 (2H, m), 2.40 (2H, q,
J=7.6 Hz), 1.10 (3H, t, J=7.6 Hz). Melting point (.degree. C.):
183-186.
EXAMPLE 303
6-Chloro-3-{3,6-dimethyl-2-[(methylsulfanyl)methyl]-phenoxy}-4-pyridazinol
(Compound No. 1083)
.sup.1H-NMR (90 MHz, CD.sub.3OD) .delta. ppm: 7.21-6.90 (2H, m),
6.71 (1H, s), 3.68 (2H, s), 2.38 (3H, s), 2.09 (3H, s), 2.00 (3H,
s). Appearance: amorphous.
EXAMPLE 304
3-[(5-Bromo-2,3-dihydro-1H-inden-4-yl)oxy]-6-chloro-4-pyridazinol
(Compound No. 1086)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.39 (1H, d, J=8.1
Hz), 7.05 (1H, d, J=8.1 Hz), 6.71 (1H, s), 2.94 (2H, t, J=7.3 Hz),
2.79 (2H, t, J=7.3 Hz), 2.10-2.00 (2H, m). Appearance:
amorphous.
EXAMPLE 305
6-Chloro-3-[(5-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-4-pyridazinol
(Compound No. 1088)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.11-7.01 (2H, m),
6.83 (1H, brs), 2.88 (3H, t, J=7.3 Hz), 2.59 (3H, t, J=7.3 Hz),
2.06 (3H, s), 2.06-1.91 (2H, m). Melting point (.degree. C.):
222-225.
EXAMPLE 306
6-Chloro-3-[(5-ethyl-2,3-dihydro-1H-inden-4-yl)oxy]-4-pyridazinol
(Compound No. 1089)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.06 (2H, s), 6.71
(1H, S) 2.91 (2H, t, J=7.3 Hz), 2.67 (2H, t, J=7.3 Hz), 2.51 (2H,
q, J=7.7 Hz), 2.04 (2H, quintet, J=7.3 Hz), 1.13 (3H, t, J=7.7 Hz).
Melting point (.degree. C.): 193-196.
EXAMPLE 307
6-Chloro-3-[(5-cyclopropyl-2,3-dihydro-1H-inden-4-yl)oxy]-4-pyridazinol
(Compound No. 1091)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.02 (1H, d, J=7.7
Hz), 6.79 (1H, d, J=7.7 Hz), 6.71 (1H, s), 2.90 (2H, t, J=7.3 Hz),
2.72 (2H, t, J=7.3 Hz), 2.18-1.98 (2H, m), 1.92-1.75 (1H, m),
0.82-0.70 (2H, m), 0.60-0.47 (2H, m). Melting point (.degree. C.):
218-220.
EXAMPLE 308
6-Chloro-3-[(6-methyl-2,3-dihydro-1-benzofuran-7-yl)oxy]-4-pyridazinol
(Compound No. 1096)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.99 (1H, d, J=7.7
Hz), 6.72 (1H, d, J=7.7 Hz), 6.70 (1H, s), 4.53 (2H, t, J=8.8 Hz),
3.20 (2H, br.t, J=8.8 Hz), 2.15 (3H, s). Melting point (.degree.
C.): 217-219.
EXAMPLE 309
3-[(6-Bromo-1-benzofuran-7-yl)oxy]-6-chloro-4-pyridazinol (Compound
No. 1099)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.75 (1H, d, J=2.2
Hz), 7.48 (1H, d, J=8.4 Hz), 7.47 (1H, d, J=8.4 Hz), 6.92 (1H, d,
J=2.2 Hz), 6.78 (1H, s) Appearance: amorphous.
EXAMPLE 310
6-Chloro-3-[(6-methyl-1-benzofuran-7-yl)oxy]-4-pyridazinol
(Compound No. 1100)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.65 (1H, d, J=2.2
Hz), 7.40 (1H, d, J=8.1 Hz), 7.14 (1H, d, J=8.1 Hz), 6.82 (1H, d,
J=2.2 Hz), 6.75 (1H, s), 2.31 (3H, s). Appearance: oily
product.
EXAMPLE 311
6-Chloro-3-[(6-cyclopropyl-1-benzofuran-7-yl)oxy]-4-pyridazol
(Compound No. 1102)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.65 (1H, d, J=2.2
Hz), 7.40 (1H, d, J=8.1 Hz), 6.87 (1H, d, J=8.1 Hz), 6.81 (1H, d,
J=2.2 Hz), 6.75 (1H, s), 2.10-1.98 (1H, m), 0.98-0.80 (2H, m),
0.80-0.64 (2H, m) Melting point (.degree. C.): 175-180.
EXAMPLE 312
6-Chloro-3-[(5-methyl-1-benzofuran-4-yl)oxy]-4-pyridazinol
(Compound No. 1109)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.65 (1H, d, J=2.2
Hz), 7.32 (1H, d, J=8.4 Hz), 7.18 (1H, d, J=8.4 Hz), 6.73 (1H, s),
6.60 (1H, d, J=2.2 Hz), 2.23 (3H, s). Melting point (.degree. C.):
222-225.
EXAMPLE 313
6-Chloro-3-(2,4-dicyclopropyl-6-fluorophenoxy)-4-pyridazinol
(Compound No. 1115)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.71-6.65 (2H, m),
6.54 (1H, s), 2.02-1.81 (2H, m), 1.01-0.72 (4H, m), 0.68-0.60 (4H,
m). Appearance: amorphous.
EXAMPLE 314
6-Chloro-3-(2,4-dibromo-3,6-dimethylphenoxy)-4-pyridazinol
(Compound No. 1118)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.54 (1H, s), 6.71
(1H, s), 2.56 (3H, s), 2.16 (3H, s). Melting point (.degree. C.):
241-248.
EXAMPLE 315
3-(2-Bromo-4,6-dimethylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 1119)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.31 (1H, brs), 7.10
(1H, brs), 6.74 (1H, s), 2.31 (3H, s), 2.17 (3H, s). Melting point
(.degree. C.): 254-256.
EXAMPLE 316
6-Chloro-3-(2-ethyl-4,6-diiodophenoxy)-4-pyridazinol (Compound No.
1120)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.03 (1H, d, J=2.2
Hz), 7.66 (1H, d, J=2.2 Hz), 6.74 (1H, s), 2.52 (2H, q, J=7.7 Hz),
1.17 (3H, t, J=7.7 Hz). Melting point (.degree. C.): 142-144.
EXAMPLE 317
6-Chloro-3-(2,4,6-trimethylphenoxy)-4-pyridazinol (Compound No.
1122)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.90 (2H, s), 6.71
(1H, s), 2.27 (3H, s), 2.07 (6H, s). Melting point (.degree. C.):
235-239.
EXAMPLE 318
6-Chloro-3-(2-cyclopropyl-4,6-dimethylphenoxy)-4-pyridazinol
(Compound No. 1123)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.88 (1H, brs), 6.69
(1H, s), 6.63 (1H, brs), 2.26 (3H, s), 2.09 (3H, s), 1.85-1.70 (1H,
m), 0.80-0.65 (2H, m), 0.65-0.50 (2H, m). Melting point (.degree.
C.): 215-217.
EXAMPLE 319
3-(2-Bromo-3,5,6-trimethylphenoxy)-6-chloro-4-pyridazinol (Compound
No. 1124)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.13 (1H, s), 6.88
(1H, brs), 2.32 (3H, s), 2.23 (3H, s), 2.01 (3H, s). Melting point
(.degree. C.): 280-290.
EXAMPLE 320
6-Chloro-3-(2,3,5,6-tetramethylphenoxy)-4-pyridazinol (Compound No.
1125)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.88 (1H, s), 6.69
(1H, s), 2.22 (6H, s), 1.98 (6H, s). Melting point (.degree. C.):
278-283.
EXAMPLE 321
6-Chloro-3-[(5,6-dimethyl-2,3-dihydro-1H-inden-4-yl)oxy]-4-pyridazinol
(Compound No. 1129)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.72 (1H, s), 6.68
(1H, s), 2.88 (2H, t, J=7.4 Hz), 2.70 (2H, t, J=7.4 Hz), 2.24 (3H,
s), 2.17 (3H, s), 2.05 (2H, quintet, J=7.4 Hz). Melting point
(.degree. C.): 210-213.
EXAMPLE 322
6-Chloro-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yloxy)-4-pyridazinol
(Compound No. 1133)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.95 (1H, s), 6.65
(1H, s), 2.88 (4H, t, J=7.3 Hz), 2.68 (4H, t, J=7.3 Hz), 2.20-1.90
(4H, m). Appearance: amorphous.
EXAMPLE 323
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl acetate (Compound
No. 1140)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.40 (1H, s),
7.26-6.98 (4H, m), 2.40 (3H, s), 1.93-1.76 (1H, m), 0.85-0.59 (4H,
m). Appearance: amorphous.
EXAMPLE 324
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl acetate
(Compound No. 1151)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.39 (1H, s),
7.15-7.00 (2H, m), 6.90-6.75 (1H, m), 2.42 (3H, s), 2.12 (3H, s),
1.90-1.67 (1H, m), 0.85-0.50 (4H, m). Melting point (.degree. C.):
98-101.
EXAMPLE 325
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl pivalate
(Compound No. 1207)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.38 (1H, s),
7.15-7.05 (2H, m), 6.90-6.84 (1H, m), 2.13 (3H, s), 1.81-1.65 (1H,
m), 1.41 (9H, s), 0.90-0.50 (4H, m). Melting point (.degree. C.):
84-87.
EXAMPLE 326
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl decanoate
(Compound No. 1251)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.38 (1H, s),
7.15-7.05 (2H, m), 6.93-6.80 (1H, m), 2.67 (2H, t, J=7.3 Hz), 2.12
(3H, s), 1.85-1.65 (3H, m), 1.55-1.10 (12H, m), 0.95-0.80 (3H, m),
0.80-0.65 (2H, m), 0.65-0.52 (2H, m). Appearance: oily product.
EXAMPLE 327
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl
cyclopropanecarboxylate (Compound No. 1266)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.43 (1H, s),
7.22-6.98 (4H, m), 2.00-1.75 (2H, m), 1.30-1.08 (4H, m), 0.86-0.51
(4H, m). Melting point (.degree. C.): 122-125.
EXAMPLE 328
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl benzoate (Compound No.
1387)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.23-8.18 (2H, m),
7.75-7.50 (3H, m), 7.60 (1H, s) 7.30-7.08 (4H, m), 2.18 (3H, s).
Appearance: oily product.
EXAMPLE 329
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl benzoate (Compound
No. 1391)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.20 (2H, d, J=7.3
Hz), 7.74-7.50 (4H, m), 7.26-7.01 (3H, m), 6.98-6.97 (1H, m),
1.91-1.80 (1H, m), 0.83-0.57 (4H, m). Appearance: amorphous.
EXAMPLE 330
6-Chloro-3-[4-(trimethylsilyl)phenoxy]-4-pyridazinyl benzoate
(Compound No. 1396)
Melting point (.degree. C.): 100-102.
EXAMPLE 331
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl benzoate
(Compound No. 1417)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.24-8.20 (2H, m),
7.75-7.68 (2H, m), 7.67-7.52 (3H, m), 7.09-7.07 (2H, m), 6.87-6.82
(1H, m), 2.16 (3H, s), 1.82-1.71 (1H, m), 0.75-0.71 (2H, m),
0.62-0.53 (2H, m) Appearance: amorphous.
EXAMPLE 332
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 2-methylbenzoate
(Compound No. 1446)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.35-8.08 (2H, m),
7.59 (1H, s), 7.68-7.00 (6H, m), 2.70 (3H, s), 2.21 (3H, s).
Melting point (.degree. C.): 91-93.
EXAMPLE 333
6-Chloro-3-(2-isopropylphenoxy)-4-pyridazinyl 2-methylbenzoate
(Compound No. 1448)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.15-8.00 (2H, m),
7.58 (1H, s), 7.75-6.90 (6H, m), 3.40-2.85 (1H, m), 2.69 (3H, s),
1.15 (6H, d, J=7.0 Hz).
Refractive index: n.sub.D.sup.22 1.5709.
EXAMPLE 334
3-(2-s-Butylphenoxy)-6-chloro-4-pyridazinyl 2-methylbenzoate
(Compound No. 1450)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.28-8.05 (1H, m),
7.60-7.05 (7H, m), 7.52 (1H, s), 3.05-2.60 (1H, m), 2.65 (3H, s),
1.70-1.00 (2H, m), 1.10 (3H, d, J=7.0 Hz), 0.90-0.50 (3H, m).
Appearance: paste state.
EXAMPLE 335
6-Chloro-3-(2-cyclohexylphenoxy)-4-pyridazinyl 2-methylbenzoate
(Compound No. 1455)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.30-7.00 (8H, m),
7.54 (1H, s), 2.68 (1H, brs), 2.67 (3H, s), 2.00-1.00 (10H, m).
Melting point (.degree. C.): 89-91.
EXAMPLE 336
3-([1,1'-Biphenyl]-2-yloxy)-6-chloro-4-pyridazinyl 2-methylbenzoate
(Compound No. 1456)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.20-7.90 (1H, m),
7.60-7.10 (13H, m), 2.58 (3H, s).
Refractive index: n.sub.D.sup.28 1.6055.
EXAMPLE 337
3-(3-tert-Butylphenoxy)-6-chloro-4-pyridazinyl 2-methylbenzoate
(Compound No. 1457)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.28-8.02 (1H, m),
7.55 (1H, s), 7.65-6.85 (7H, m), 2.64 (3H, s), 1.28 (9H, s).
Melting point (.degree. C.): 63-64.
EXAMPLE 338
6-Chloro-3-(3-methoxyphenoxy)-4-pyridazinyl 2-methylbenzoate
(Compound No. 1458)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.30-8.00 (1H, m),
7.70-7.10 (4H, m), 7.55 (1H, s), 6.90-6.60 (3H, m), 3.74 (3H, s),
2.64 (3H, s). Melting point (.degree. C.): 66-67.
EXAMPLE 339
6-Chloro-3-(2-isopropyl-5-methylphenoxy)-4-pyridazinyl
2-methylbenzoate (Compound No. 1459)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.30-8.00 (1H, m),
7.54 (1H, s), 7.50-6.80 (6H, m), 3.30-2.75 (1H, m), 2.65 (3H, s),
2.28 (3H, s), 1.15 (6H, d, J=7.00 Hz). Melting point (.degree. C.):
95-97.
EXAMPLE 340
6-Chloro-3-(1-naphthyloxy)-4-pyridazinyl 2-methylbenzoate (Compound
No. 1461)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.20-7.00 (12H, m),
2.65 (3H, s) Melting point (.degree. C.): 133-134.
EXAMPLE 341
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 2-methoxybenzoate
(Compound No. 1509)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.11-7.89 (2H, m),
7.70-6.80 (6H, m), 7.50 (1H, s), 3.84 (3H, s), 2.10 (3H, s).
Melting point (.degree. C.): 114-116.
EXAMPLE 342
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 4-methylbenzoate
(Compound No. 1553)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.07 (2H, d, J=8.0
Hz), 7.58 (1H, s), 7.40-7.03 (4H, m), 7.36 (2H, d, J=8.0 Hz), 2.51
(3H, s), 2.23 (3H, s). Melting point (.degree. C.): 105-108.
EXAMPLE 343
6-Chloro-3-(2-isopropylphenoxy)-4-pyridazinyl 4-methylbenzoate
(Compound No. 1554)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.28-7.82 (2H, m),
7.61 (1H, s), 7.51-6.90 (6H, m), 3.30-2.80 (1H, m), 2.46 (3H, s),
1.19 (6H, d, J=7.0 Hz).
Refractive index: n.sub.D.sup.22 1.5731.
EXAMPLE 344
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 2,4-dichlorobenzoate
(Compound No. 1603)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.04 (1H, d, J=8.4
Hz), 7.58 (1H, s), 7.58-6.92 (6H, m), 2.20 (3H, s). Melting point
(.degree. C.): 81-82.5.
EXAMPLE 345
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl methyl carbonate
(Compound No. 1658)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.51 (1H, s),
7.23-6.98 (4H, m), 3.99 (3H, s), 1.91-1.82 (1H, m), 0.84-0.61 (4H,
m). Appearance: amorphous.
EXAMPLE 346
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl ethyl carbonate
(Compound No. 1706)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.51 (1H, s),
7.38-7.00 (4H, m), 4.40 (2H, q, J=7.0 Hz), 2.20 (3H, s), 1.40 (3H,
t, J=7.0 Hz). Melting point (.degree. C.): 73-74.
EXAMPLE 347
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl ethyl carbonate
(Compound No. 1710)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.51 (1H s),
7.26-6.98 (4H, m), 4.40 (2H, q, J=7.0 Hz), 1.90-1.80 (1H, m), 1.41
(3H, t, J=7.0 Hz), 0.84-0.60 (4H, m). Appearance: amorphous.
EXAMPLE 348
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl isobutyl carbonate
(Compound No. 1757)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.45 (1H, s),
7.30-7.00 (4H, m), 4.08 (2H, d, J=5.8 Hz), 2.16 (3H, s), 2.20-1.70
(1H, m), 0.96 (6H, d, J=5.8 Hz). Melting point (.degree. C.):
46-47.
EXAMPLE 349
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 2,2,2-trichloroethyl
carbonate (Compound No. 1789)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.52 (1H, s),
7.28-7.03 (4H, m), 4.94 (2H, s), 2.18 (3H, s). Appearance:
amorphous.
EXAMPLE 350
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl phenyl
carbonate (Compound No. 1840)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.50-7.20 (5H, m), 7.20-7.05 (2H, m), 6.92-6.82 (1H, m), 2.16 (3H,
s), 1.88-1.72 (1H, m), 0.80-0.55 (4H, m). Appearance: oily
product.
EXAMPLE 351
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl dimethylcarbamate
(Compound No. 1877)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.55 (1H, s),
7.40-6.92 (4H, m), 3.10 (3H, s), 3.01 (3H, s), 2.19 (3H, s).
Melting point (.degree. C.): 107-109.
EXAMPLE 352
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl dimethylcarbamate
(Compound No. 1879)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.22-6.98 (4H, m), 3.13 (3H, s), 3.04 (3H, s), 1.97-1.80 (1H, m),
0.85-0.63 (4H, m). Melting point (.degree. C.): 137-138.
EXAMPLE 353
6-Chloro-3-[3-(trifluoromethyl)phenoxy]-4-pyridazinyl
dimethylcarbamate (Compound No. 1881)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.60 (1H, s),
7.65-7.22 (4H, m), 3.11 (3H s), 3.05 (3H s). Melting point
(.degree. C.): 92-93.
EXAMPLE 354
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl diethylcarbamate
(Compound No. 1898)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.55 (1H, s),
7.40-6.92 (4H, m), 3.41 (4H, q, J=6.2 Hz), 2.20 (3H, s), 1.27 (6H,
t, J=6.2 Hz). Melting point (.degree. C.): 74-75.5.
EXAMPLE 355
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 1-pyrrolidinecarboxylate
(Compound No. 1924)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.42-7.02 (4H, m), 3.67-3.37 (4H, m), 2.19 (3H, s), 2.07-1.72 (4H,
m). Melting point (.degree. C.): 126-127.
EXAMPLE 356
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl methanesulfonate
(Compound NO. 1981)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.55 (1H, s),
7.33-7.06 (4H, m), 3.43 (3H, s), 2.20 (3H, s) Appearance: oily
product.
EXAMPLE 357
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl methanesulfonate
(Compound No. 1985)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.55 (1H, s),
7.26-7.23 (2H, m), 7.21-7.02 (2H, m), 3.44 (3H, s), 1.89-1.80 (1H,
m), 0.86-0.61 (4H, m) Melting point (.degree. C.): 162-172.
EXAMPLE 358
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
methanesulfonate (Compound No. 2010)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56 (1H, s),
7.18-7.09 (2H, m), 6.91-6.86 (1H, m), 3.47 (3H, s), 2.16 (3H, s),
1.82-1.68 (1H, m), 0.75-0.69 (2H, m), 0.67-0.55 (2H, m).
Appearance: amorphous.
EXAMPLE 359
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 1-propanesulfonate
(Compound No. 2038)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.34-7.05 (4H, m), 3.48 (2H, t, J=7.7 Hz), 2.20 (3H, s), 2.10 (2H,
sixtet, J=7.7 Hz), 1.14 (3H, t, J=7.7 Hz). Melting point (.degree.
C.): 72-73.
EXAMPLE 360
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl 1-propanesulfonate
(Compound No. 2040)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.28-7.15 (2H, m), 7.12-6.99 (2H, m), 3.52-3.45 (2H, m), 2.17-1.98
(2H, m), 1.92-1.78 (1H, m), 1.11 (3H, t, J=7.3 Hz), 0.85-0.73 (2H,
m), 0.69-0.60 (2H, m). Appearance: paste state.
EXAMPLE 361
6-Chloro-3-(2,3-dihydro-1H-inden-4-yloxy)-4-pyridazinyl
1-propanesulfonate (Compound No. 2042)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56 (1H, s),
7.26-7.14 (2H, m), 6.94 (1H, dd, J=7.0, 1.8 Hz), 3.50-3.42 (2H, m),
2.98 (2H, t, J=7.3 Hz), 2.74 (2H, t, J=7.3 Hz), 2.17-1.98 (4H, m),
1.12 (3H, t, J=7.3 Hz). Appearance: paste state.
EXAMPLE 362
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-5-iodo-4-pyridazinol
(Compound No. 3849)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.08-7.05 (2H, m),
6.84-6.80 (1H, m), 2.14 (3H, s), 1.86-1.75 (1H, m), 0.81-0.65 (2H,
m), 0.60-0.52 (2H, m) Appearance: amorphous.
EXAMPLE 363
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
trifluoromethanesulfonate (Compound No. 2106)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.52 (1H, s),
7.19-7.09 (2H, m), 6.96-6.89 (1H, m), 2.15 (3H, s), 1.81-1.67 (1H,
m), 0.73-0.58 (4H, m) Melting point (.degree. C.): 64-67.
EXAMPLE 364
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl benzenesulfonate
(Compound No. 2147)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.10-7.83 (2H, m),
7.80-7.40 (3H, m), 7.59 (1H, s), 7.30-7.00 (3H, m), 6.90-6.60 (1H,
m). Melting point (.degree. C.): 91.5-92.
EXAMPLE 365
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl benzenesulfonate
(Compound No. 2151)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.02-7.98 (2H, m),
7.78-7.70 (1H, m), 7.62-7.54 (2H, m), 7.58 (1H, s), 7.26-7.09 (2H,
m), 6.98-6.93 (1H, m), 6.78-6.69 (1H, m), 1.68-1.54 (1H, m),
0.74-0.52 (4H, m). Appearance: oily product.
EXAMPLE 366
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
benzenesulfonate (Compound No. 2176)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.07-8.01 (2H, m),
7.80-7.71 (1H, m), 7.65-7.56 (2H, m), 7.60 (1H, s), 7.11-6.99 (2H,
m), 6.80 (1H, dd, J=4.4, 2.4 Hz), 1.93 (3H, s), 1.61-1.45 (1H, m),
0.65-0.45 (4H, m). Melting point (.degree. C.): 105-106.
EXAMPLE 367
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 4-chlorobenzenesulfonate
(Compound No. 2198)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.94 (2H, d, J=8.4
Hz), 7.60 (1H, s), 7.59 (2H, d, J=8.4 Hz), 7.23-7.09 (3H, m),
6.90-6.60 (1H, m), 2.93 (3H, s). Melting point (.degree. C.):
93-94.
EXAMPLE 368
3-(2-Isopropylphenoxy)-4-pyridazinyl 4-chlorobenzenesulfonate
(Compound No. 2199)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.91 (2H, d, J=8.4
Hz), 7.62 (1H, s), 7.55 (2H, d, J=8.4 Hz), 7.50-7.00 (3H, m),
6.80-6.60 (1H, m), 3.20-2.50 (1H, m), 1.14 (6H, d, J=7.0 Hz).
Refractive index: n.sub.D.sup.22 1.5315.
EXAMPLE 369
3-(2-tert-Butylphenoxy)-6-chloro-4-pyridazinyl
4-chlorobenzenesulfonate (Compound No. 2200)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.05-7.05 (8H, m),
6.70-6.40 (1H, m), 1.26. (9H, s) Melting point (.degree. C.):
83.5-84.5.
EXAMPLE 370
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 4-methylbenzenesulfonate
(Compound No. 2220)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.83 (2H, d, J=8.4
Hz), 7.47 (2H, d, J=8.4 Hz), 7.32-6.95 (4H, m), 6.85-6.55 (1H, m),
2.43 (3H, s), 1.98 (3H, s). Melting point (.degree. C.):
102-104.
EXAMPLE 371
6-Chloro-3-(2-ethylphenoxy)-4-pyridazinyl 4-methylbenzenesulfonate
(Compound No. 2221)
Refractive index: n.sub.D.sup.28 1.5847.
EXAMPLE 372
6-Chloro-3-(2-isopropylphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2222)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.00-6.50 (8H, m),
7.55 (1H, s), 2.85 (1H, septet, J=7.0 Hz), 2.42 (3H, s), 1.11 (6H,
d, J=7.0 Hz). Melting point (.degree. C.): 99-100.
EXAMPLE 373
3-(2-s-Butylphenoxy)-6-chloro-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2223)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.98-6.50 (8H, m),
7.52 (1H, s), 2.99-2.31 (1H, m), 2.41 (3H, s), 1.82-0.95 (2H, m),
1.08 (3H, d, J=7.0 Hz), 0.90-0.35 (3H, m). Melting point (.degree.
C.): 65-66.
EXAMPLE 374
3-(2-tert-Butylphenoxy)-6-chloro-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2224)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.98-7.00 (7H, m),
7.61 (1H s), 6.78-6.45 (1H, m), 2.40 (3H, s), 1.29 (9H, s). Melting
point (.degree. C.): 98-99.
EXAMPLE 375
5,6-Dichloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol
(Compound No. 3837)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.08-7.06 (2H, m),
6.85-6.80 (1H, m), 2,14 (3H, s), 1.87-1.78 (1H, m), 0.81-0.72 (2H,
m), 0.64-0.52 (2H, m) Appearance: amorphous.
EXAMPLE 376
6-Chloro-3-(2-cyclohexylphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2230)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.00-6.50 (8H, m),
7.50 (1H, s), 2.50 (1H, brs), 2.40 (3H, s), 2.00-0.90 (1OH, m).
Melting point (.degree. C.): 120-121.
EXAMPLE 377
3-([1,1'-Biphenyl]-2-yloxy)-6-chloro-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2231)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.80-6.60 (14H, m),
2.42 (3H, s). Melting point (.degree. C.): 106-108.
EXAMPLE 378
6-Chloro-3-(2-methoxyphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2232)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.00-6.70 (8H, m),
7.56 (1H, s), 3.62 (3H, s), 2.44 (3H, s). Melting point (.degree.
C.): 153-157.
EXAMPLE 379
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl propionate
(Compound No. 1160)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.39 (1H, s),
7.14-7.05 (2H, m), 6.89-6.82 (1H, m), 2.72 (2H, q, J=7.6 Hz), 2.12
(3H, s), 1.82-1.68 (1H, m), 1.31 (3H, t, J=7.6 Hz), 0.77-0.53 (4H,
m). Melting point (.degree. C.): 75-77.
EXAMPLE 380
6-Chloro-3-(3-chlorophenoxy)-4-pyridazinyl 4-methylbenzenesulfonate
(Compound No. 2234)
Refractive index: n.sub.D.sup.28 1.5970.
EXAMPLE 381
3-(3-tert-Butylphenoxy)-6-chloro-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2235)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.73 (2H, d, J=8.2
Hz), 7.49 (1H, s), 7.23 (2H, d, J=8.2 Hz), 7.14 (1H, d, J=4.0 Hz),
6.90-6.45 (3H, m), 2.38 (3H, s), 1.26 (9H, s). Melting point
(.degree. C.): 56-57.
EXAMPLE 382
6-Chloro-3-[3-(trifluoromethyl)phenoxy]-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2236)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.95-6.93 (9H, m),
2.40 (3H, s).
Refractive index: n.sub.D.sup.25.5 1.5556.
EXAMPLE 383
6-Chloro-3-(3-cyanophenoxy)-4-pyridazinyl 4-methylbenzenesulfonate
(Compound No. 2237)
.sup.1H-NMR (90 MHz, CDCl.sub.3) .delta. ppm: 7.85 (2H, d, J=8.0
Hz), 7.70-7.00 (7H, m), 2.49 (3H, s). Appearance: paste state.
EXAMPLE 384
6-Chloro-3-(3-methoxyphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2238)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.90-6.30 (8H, m),
7.47 (1H, s), 3.71 (3H, s), 2.40 (3H, s). Melting point (.degree.
C.): 89-90.
EXAMPLE 385
6-Chloro-3-(1-naphthyloxy)-4-pyridazinyl 4-methylbenzenesulfonate
(Compound No. 2240)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.90-6.80 (12H, m),
2.38 (3H, s). Melting point (.degree. C.): 92-94.
EXAMPLE 386
3-(2-Bromo-4-tert-butylphenoxy)-6-chloro-6-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2245)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.89 (2H, d, J=8.4
Hz), 7.63 (1H, s), 7.62-7.18 (3H, m), 6.84 (2H, d, J=8.4 Hz), 2.43
(3H, s), 1.29 (9H, s) Melting point (.degree. C.): 110-112.
EXAMPLE 387
6-Chloro-3-(4-chloro-2-methylphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2246)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.95-7.75 (2H, m),
7.60-7.00 (5H, m), 6.80-6.60 (1H, m), 2.46 (3H, s), 2.00 (3H, s).
Melting point (.degree. C.): 115-116.
EXAMPLE 388
6-Chloro-3-(2,4-dimethylphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2247)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.94-7.78 (2H, m),
7.54 (1H, s), 7.41-7.23 (2H, m), 7.02-6.53 (3H, m), 2.46 (3H, s),
2.30 (3H, s), 1.96 (3H, s). Melting point (.degree. C.): 80-81.
EXAMPLE 389
3-(4-Bromo-2-isopropylphenoxy)-6-chloro-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2248)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.80 (2H, d, J=8.4
Hz), 7.51 (1H, s), 7.45-7.10 (3H, m), 6.56 (2H, d, J=8.4 Hz), 2.85
(1H, septet, J=6.8 Hz), 2.43 (3H, s), 1.10 (6H, d, J=6.8 Hz).
Melting point (.degree. C.): 119-122.
EXAMPLE 390
6-Chloro-3-(2-isopropyl-5-methylphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2249)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.00-6.80 (6H, m),
7.56 (1H, s), 6.46 (1H, brs), 2.95-2.50 (1H, m), 2.44 (3H, s), 2.25
(3H, s), 1.09. (6H, d, J=7.0 Hz). Melting point (.degree. C.):
90-92.
EXAMPLE 391
6-Chloro-3-(2,6-dimethylphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2263) Melting point
(.degree. C.): 89-90.
EXAMPLE 392
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methylbenzenesulfonate (Compound No. 2265)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.90 (2H, d, J=8.1
Hz), 7.60 (1H, s), 7.38 (2H, d, J=8.1 Hz), 7.11-7.01 (2H, m), 6.80
(1H, dd, J=6.6, 2.6 Hz), 2.47 (3H, s), 1.93 (3H, s), 1.59-1.46 (1H,
m), 0.64-0.45 (4H, m). Melting point (.degree. C.): 85-87.
EXAMPLE 393
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl 4-nitrobenzenesulfonate
(Compound No. 2287)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 8.41 (2H, d, J=8.4
Hz), 8.33 (2H, d, J=8.4 Hz), 7.61 (1H, s), 7.30-7.02 (3H, m),
6.95-6.63 (1H, m), 2.03 (3H, s). Melting point (.degree. C.):
166-169.
EXAMPLE 394
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl
4-nitrobenzenesulfonate (Compound No. 2289)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.39 (2H, d, J=8.8
Hz), 8.23 (2H, d, J=8.8 Hz), 7.59 (1H, s), 7.20-7.09 (2H, m),
6.97-6.92 (1H, m), 6.77-6.73 (1H, m), 1.67-1.59 (1H, m), 0.78-0.54
(4H, m). Melting point (.degree. C.): 158.
EXAMPLE 395
6-Chloro-3-(2-cyclopropylphenoxy)-4-pyridazinyl dimethylsulfamate
(Compound No. 2351)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.60 (1H, s),
7.26-7.01 (4H, m), 3.09 (6H, s), 1.95-1.78 (1H, m), 0.85-0.63 (4H,
m). Appearance: oily product.
EXAMPLE 396
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-methylpropanoate (Compound No. 1172)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.38 (1H, s),
7.14-7.05 (2H, m), 6.90-6.83 (1H, m), 2.93 (1H, septet, J=7.0 Hz),
2.13 (3H, s), 1.80-1.66 (1H, m), 1.36 (6H, d, J=7.0 Hz), 0.78-0.56
(4H, m). Melting point (.degree. C.): 38-39.
EXAMPLE 397
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl pentanoate
(Compound No. 1178)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.38 (1H, s),
7.13-7.00 (2H, m), 6.90-6.77 (1H, m), 2.68 (2H, t, J=7.3 Hz), 2.12
(3H, s), 1.88-1.65 (3H, m), 1.60-1.35 (2H, m), 0.95 (3H, t, J=7.3
Hz), 0.80-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 398
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-methylbutanoate (Compound No. 1184)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.37 (1H, s),
7.14-7.07 (2H, m), 6.89-6.82 (1H, m), 2.55 (2H, d, J=7.0 Hz), 2.27
(1H, br.septet, J=6.8 Hz), 2.12 (3H, s), 1.80-1.67 (1H, m), 1.07
(6H, d, J=6.6 Hz), 0.77-0.55 (4H, m). Melting point (.degree. C.):
71-74.
EXAMPLE 399
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
pentadecanoate (Compound No. 1260)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.37 (1H, s),
7.10-7.00 (2H, m), 6.87-6.77 (1H, m), 2.66 (2H, t, J=6.4 Hz), 2.12
(3H, s), 1.85-1.65 (3H, m), 1.35-1.18 (22H, m), 0.95-0.82 (3H, m),
0.80-0.50 (4H, m). Melting point (.degree. C.): 35-37.
EXAMPLE 400
6-Chloro-3-phenoxy-5-(trimethylsilyl)-4-pyridazinol (Compound No.
2402)
.sup.1H-NMR (90 MHz, CDCl.sub.3) .delta. ppm: 12.0 (1H, brs),
7.30-6.81 (5H, m), 0.28 (9H, s). Melting point (.degree. C.):
119-120.
EXAMPLE 401
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
cyclobutanecarboxylate (Compound No. 1286)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.38 (1H, s),
7.14-7.05 (2H, m), 6.89-6.79 (1H, m), 3.58-3.40 (1H, m), 2.60-1.85
(6H, m), 2.13 (3H, s), 1.82-1.67 (1H, m), 0.80-0.67 (2H, m),
0.64-0.53 (2H, m). Appearance: paste state.
EXAMPLE 402
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
cyclohexanecarboxylate (Compound No. 1298)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.37 (1H, s),
7.15-7.05 (2H, m), 6.90-6.80 (1H, m), 2.78-2.60 (1H, m), 2.12 (3H,
s), 1.90-1.20 (1OH, m), 0.80-0.50 (4H, m). Melting point (.degree.
C.): oily product.
EXAMPLE 403
3-(2-Isopropylphenoxy)-6-methyl-4-pyridazinol (Compound No.
2418)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.40-7.35 (1H, m),
7.25-7.16 (2H, m), 7.04-6.98 (1H, m), 6.43 (1H, s), 3.06 (1H,
septet, J=7.0 Hz), 2.36 (3H, s), 1.18 (6H, d, J=7.0 Hz). Melting
point (.degree. C.): 259-260.
EXAMPLE 404
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-bromobutanoate (Compound No. 1334)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.44 (1H, s),
7.14-7.05 (2H, m), 6.90-6.83 (1H, m), 4.45 (1H, t, J=7.6 Hz), 2.22
(1H, dq, J=7.3, 7.6 Hz), 2.13 (3H, s), 1.81-1.69 (1H, m), 1.17 (3H,
t, J=7.3 Hz), 0.74-0.69 (2H, m), 0.58-0.56 (2H, m). Appearance:
paste state.
EXAMPLE 405
3-(2-Isopropylphenoxy)-6-(trifluoromethyl)-4-pyridazinol (Compound
No. 2431)
.sup.1H-NMR (60 MHz, CDCl.sub.3) .delta. ppm: 7.60-6.70 (4H, m),
6.87 (1H, s), 2.97 (1H, septet, J=7.0 Hz), 1.10 (6H, d, J=7.0 Hz).
Melting point (.degree. C.): 126.5.
EXAMPLE 406
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-chlorobutanoate (Compound No. 1340)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.40 (1H, s),
7.14-7.05 (2H, m), 6.89-6.82 (1H, m), 3.68 (2H, t, J=6.2 Hz), 2.91
(2H, t, J=7.0 Hz), 2.31-2.18 (2H, m), 2.11 (3H, s), 1.79-1.65 (1H,
m), 0.80-0.67 (2H, m), 0.63-0.53 (2H, m). Appearance: paste
state.
EXAMPLE 407
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-methyl-2-butenoate (Compound No. 1358)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.44 (1H, s),
7.12-7.05 (2H, m), 6.88-6.80 (1H, m), 5.99-5.97 (1H, m), 2.26 (3H,
d, J=1.1 Hz), 2.13 (3H, s) 2.04 (3H, d, J=1.1 Hz), 1.83-1.70 (1H,
m), 0.77-0.64 (2H, m), 0.60-0.53 (2H, m). Appearance: paste
state.
EXAMPLE 408
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
(2E)-3-phenyl-2-propenoate (Compound No. 1364)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.96 (1H, d, J=16.0
Hz), 7.63-7.59 (2H, m), 7.53 (1H, s), 7.48-7.43 (3H, m), 7.09-7.05
(2H, m), 6.86-6.81 (1H, m), 6.66 (1H, d, J=16.0 Hz), 2.16 (3H, s),
1.83-1.75 (1H, m), 0.79-0.54 (4H, m). Appearance: amorphous.
EXAMPLE 409
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl methyl
succinate (Compound No. 1382)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.44 (1H, s),
7.08-7.02 (2H, m), 6.88-6.74 (1H, m), 3.69 (3H, s), 3.01 (2H, t,
J=7.3 Hz), 2.78 (2H, t, J=7.3 Hz), 2.11 (3H, s), 1.85-1.65 (1H, m),
0.80-0.50 (4H, m). Appearance: oily product.
EXAMPLE 410
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-chlorobenzoate (Compound No. 1441)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.14 (1H, d, J=8.8
Hz), 7.58 (1H, s), 7.59-7.39 (3H, m), 7.10-7.05 (2H, m), 6.88-6.80
(1H, m), 2.16 (3H, s), 1.90-1.70 (1H, m), 0.85-0.50 (4H, m).
Appearance: oily product.
EXAMPLE 411
3-(2-Methylphenoxy)-6-(2-thienyl)-4-pyridazinol (Compound No.
2478)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56-7.48 (2H, m),
7.21-7.00 (4H, m), 6.97-6.90 (1H, m), 6.69 (1H, s), 2.11 (3H, s).
Melting point (.degree. C.): 86-87.
EXAMPLE 412
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-methylbenzoate (Compound No. 1481)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.20 (1H, d, J=7.0
Hz), 7.56 (1H, s), 7.52 (1H, d, J=7.7 Hz), 7.40-7.28 (2H, m),
7.10-7.00 (2H, m), 6.90-6.88 (1H, m), 2.69 (3H, s), 2.16 (3H, s),
1.90-1.70 (1H, m), 0.82-0.65 (2H, m), 0.65-0.50 (2H, m).
Appearance: oily product.
EXAMPLE 413
3,6-Bis(2-methylphenoxy)-4-pyridazinol (Compound No. 2492)
.sup.1H-NMR (60 MHz, DMF-d.sub.7) .delta. ppm: 7.40-6.90 (8H, m),
5.79 (1H, s), 2.19 (6H, brs) Melting point (.degree. C.):
247-250.
EXAMPLE 414
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-methoxybenzoate (Compound No. 1522)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.09 (1H, dd, J=7.9,
2.0 Hz) 7.68-7.57 (1H, m), 7.59 (1H, s), 7.15-7.03 (4H, m),
6.90-6.82 (1H, m), 3.96 (3H, s), 2.17 (3H, s), 1.96-1.72 (1H, m),
0.78-0.65 (2H, m), 0.65-0.51 (2H, m). Appearance: gum state.
EXAMPLE 415
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-methylbenzoate (Compound No. 1531)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.05-8.00 (2H, m),
7.58 (1H, s), 7.55-7.38 (2H, m), 7.10-7.05 (2H, m), 6.88-6.80 (1H,
m), 2.46 (3H, s), 2.16 (3H, s), 1.90-1.68 (1H, m), 0.80-0.50 (4H,
m). Appearance: oily product.
EXAMPLE 416
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-chlorobenzoate (Compound No. 1537)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.16 (2H, d, J=8.8
Hz), 7.59 (1H, s), 7.54 (2H, d, J=8.8 Hz), 7.14-7.07 (2H, m),
6.88-6.83 (1H, m), 2.15 (3H, s), 1.84-1.69 (1H, m), 0.80-0.70 (2H,
m), 0.62-0.55 (2H, m). Appearance: amorphous.
EXAMPLE 417
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-bromobenzoate (Compound No. 1543)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.07 (2H, d, J=8.6
Hz), 7.70 (2H, d, J=8.6 Hz), 7.59 (1H, s), 7.12-7.03 (2H, m),
6.89-6.82 (1H, m), 2.15 (3H, s), 1.83-1.67 (1H, m), 0.78-0.50 (4H,
m). Appearance: amorphous.
EXAMPLE 418
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-iodobenzoate (Compound No. 1549)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.94 (2H, s), 7.93
(1H, m) 7.62 (1H, s), 7.29 (1H, s), 7.12-7.09 (2H, m), 6.89-6.87
(1H, m), 2.17 (3H, s), 1.84-1.73 (1H, m), 0.79-0.70 (2H, m),
0.62-0.55 (2H, m). Appearance: paste state.
EXAMPLE 419
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methylbenzoate (Compound No. 1566)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.10 (2H, d, J=8.1
Hz), 7.60 (1H, s), 7.34 (2H, d, J=8.1 Hz), 7.12-7.03 (2H, m),
6.88-6.81 (1H, m), 2.46 (3H, s), 2.15 (3H, s), 1.85-1.71 (1H, m),
0.78-0.65 (2H, m), 0.62-0.52 (2H, m). Melting point (.degree. C.):
77.5-78.
EXAMPLE 420
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-tert-butylbenzoate (Compound No. 1575)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.15 (2H, d, J=8.8
Hz), 7.59 (1H, s), 7.56 (2H, d, J=8.8 Hz), 7.09-7.06 (2H, m),
6.86-6.82 (1H, m), 2.15 (3H, s), 1.37 (9H, s), 1.82-1.73 (1H, m),
0.76-0.69 (2H, m), 0.60-0.56 (2H, m). Melting point (.degree. C.):
139-142.
EXAMPLE 421
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-nitrobenzoate (Compound No. 1593)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.41 (4H, s), 7.61
(1H, s) 7.14-7.08 (2H, m), 6.89-6.83 (1H, m), 2.17 (3H, s),
1.81-1.70 (1H, m), 0.80-0.71 (2H, m), 0.62-0.54 (2H, m).
Appearance: amorphous.
EXAMPLE 422
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methoxybenzoate (Compound No. 1599)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.17 (2H, d, J=8.8
Hz), 7.60 (1H, s), 7.12-7.04 (2H, m), 7.01 (2H, d, J=8.8 Hz),
6.88-6.82 (1H, m), 3.90 (1H, s), 2.16 (3H, s), 1.85-1.71 (1H, m),
0.78-0.69 (2H, m), 0.60-0.52 (2H, m). Appearance: amorphous.
EXAMPLE 423
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,4-dichlorobenzoate (Compound No. 1616)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.11 (1H, d, J=8.4
Hz), 7.60-7.57 (2H, m), 7.42 (1H, dd, J=8.4, 2.2 Hz), 7.14-7.08
(2H, m), 6.89-6.83 (1H, m), 2.15 (3H, s), 1.85-1.72 (1H, m),
0.78-0.67 (2H, m), 0.63-0.54 (2H, m). Appearance: amorphous.
EXAMPLE 424
6-Chloro-3-(2-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl phthalate
(Compound No. 1620)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.98-7.94 (1H, m),
7.88-7.84 (1H, m), 7.81-7.71 (2H, m), 7.57 (1H, s), 7.28-7.17 (6H,
m), 7.08-7.03 (1H, m), 3.70 (3H, s), 2.26 (3H, s), 2.15 (3H, s).
Appearance: amorphous.
EXAMPLE 425
Potassium
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinoate
(Compound No. 3811)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.05-6.95 (2H, m),
6.83-6.72 (1H, m), 6.47 (1H, s), 2.00-1.83 (1H, m), 0.80-0.64 (2H,
m), 0.64-0.48 (2H, m). Melting point (.degree. C.): 187-189.
EXAMPLE 426
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H -pyrazol-5-yl isophthalate
(Compound No. 1631)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.61 (1H, t, J=1.5
Hz), 8.54-8.47 (1H, m), 8.22-8.16 (1H, m), 7.71 (1H, t, J=8.1 Hz),
7.61 (1H, s), 7.15-6.96 (4H, m), 6.89-6.82 (1H, m), 3.67 (3H, s),
2.44 (3H, s), 2.17 (3H, s), 1.88-1.72 (1H, m), 0.83-0.71 (2H, m),
0.64-0.53 (2H, m). Appearance: amorphous.
EXAMPLE 427
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl 2-furoate
(Compound No. 1643)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.74-7.73 (1H, m),
7.56 (1H, s), 7.50 (1H, dd, J=3.7, 0.7 Hz), 7.13-7.04 (2H, m),
6.88-6.81 (1H, m), 6.65-6.63 (1H, m), 2.15 (3H, s), 1.85-1.71 (1H,
m), 0.78-0.69 (2H, m), 0.62-0.52 (2H, m). Appearance: paste
state.
EXAMPLE 428
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-thiophenecarboxylate (Compound No. 1649)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.07-8.05 (1H, m),
7.78-7.75 (1H, m), 7,58 (1H, s), 7.24-7.20 (1H, m), 7.13-7.06 (2H,
m), 6.89-6.83 (1H, m), 2.16 (3H, s), 1.83-1.71 (1H, m), 0.80-0.70
(2H, m), 0.65-0.55 (2H, m). Appearance: amorphous.
EXAMPLE 429
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl isobutyl
carbonate (Compound No. 1770)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.49 (1H, s),
7.15-7.05 (2H, m), 6.89-6.82 (1H, m), 4.13 (2H, d, J=6.6 Hz), 2.14
(3H, s), 2.09 (1H, br.septet, J=7.0 Hz), 1.88-1.68 (1H, m), 1.01
(6H, d, J=7.0 Hz), 0.78-0.52 (4H, m). Melting point (.degree. C.):
72-74.
EXAMPLE 430
Allyl 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
carbonate (Compound No. 1811)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.50 (1H, s),
7.15-7.06 (2H, m), 6.89-6.82 (1H, m), 6.10-5.90 (1H, m), 5.51-5.35
(2H, m), 4.84-4.80 (2H, m), 2.14 (3H, s), 1.85-1.70 (1H, m),
0.78-0.53 (4H, m). Appearance: oily product.
EXAMPLE 431
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
dimethylcarbamate (Compound No. 1891)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56 (1H s),
7.13-7.05 (2H, m), 6.89-6.82 (1H, m), 3.16 (3H, s), 3.05 (3H, s),
2.15 (3H, s), 1.85-1.71 (1H, m), 0.78-0.54 (4H, m). Melting point
(.degree. C.): 136-138.
EXAMPLE 432
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
diethylcarbamate (Compound No. 1911)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.10-7.07 (2H, m), 6.87-6.83 (1H, m), 3.48 (2H, q, J=7.3 Hz), 3.41
(2H, q, J=7.0 Hz), 2.15 (3H, s), 1.82-1.72 (1H, m), 1.29 (3H, t,
J=7.3 Hz), 1.23 (3H, t, J=7.0 Hz), 0.74-0.57 (4H, m). Melting point
(.degree. C.): 119-121.
EXAMPLE 433
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
diisopropylcarbamate (Compound No. 1920)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.61 (1H, s),
7.10-7.00 (2H, m), 6.90-6.85 (1H, m), 4.20-3.90 (2H, m), 2.14 (3H,
s), 1.87-1.67 (1H, m), 1.45-1.20 (12H, m), 0.80-0.50 (4H, m).
Melting point (.degree. C.): 103-105.
EXAMPLE 434
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-thiophenesulfonate (Compound No. 3792)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.89-7.82 (2H, m),
7.58 (1H, s), 7.22-7.13 (1H, m), 7.13-7.02 (2H, m), 6.84-6.79 (1H,
m), 1.99 (3H, s), 1.69-1.53 (1H, m), 0.70-0.48 (4H, m). Appearance:
amorphous.
EXAMPLE 435
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
methyl(phenyl)carbamate (Compound No. 1946)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.40-7.25 (6H, m),
7.11-7.08 (2H, m), 6.87-6.82 (1H, m), 3.42 (3H, br.s), 2.15 (3H,
br.s), 1.82-1.68 (1H, m), 0.71-0.56 (4H, m). Appearance:
amorphous.
EXAMPLE 436
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
diphenylcarbamate (Compound No. 1952)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.45-7.28 (11H, m),
7.16-7.09 (2H, m), 6.87-6.82 (1H, m), 2.11 (3H, s), 1.79-1.66 (1H,
m), 0.69-0.56 (4H, m). Appearance: amorphous.
EXAMPLE 437
O-[6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
S-methyl thiocarbonate (Compound No. 1958)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.47 (1H, s),
7.13-7.06 (2H, m), 6.89-6.83 (1H, m), 2.49 (3H, s), 2.14 (3H, s),
1.83-1.69 (1H, m), 0.78-0.65 (2H, m), 0.63-0.55 (2H, m).
Appearance: paste state.
EXAMPLE 438
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
ethanesulfonate (Compound No. 2034)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.15-7.05 (2H, m), 6.92-6.82 (1H, m), 3.58 (2H, q, J=7.4 Hz), 2.15
(3H, s), 1.82-1.68 (1H, m), 1.64 (3H, t, J=7.4 Hz), 0.78-0.52 (4H,
m). Melting point (.degree. C.): 96-97.
EXAMPLE 439
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-propanesulfonate (Compound No. 2051)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.18-7.05 (2H, m), 6.94-6.83 (1H, m), 3.53 (2H, t, J=7.7 Hz),
2.20-2.00 (2H, m), 2.15 (3H, s), 1.82-1.67 (1H, m), 1.15 (3H, t,
J=7.7 Hz), 0.80-0.50 (4H, m). Melting point (.degree. C.):
70.5-71.5.
EXAMPLE 440
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-propanesulfonate (Compound No. 2060)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (1H, s),
7.18-7.07 (2H, m), 6.93-6.82 (1H, m), 3.75 (1H, septet, 7.0 Hz),
2.15 (3H, S), 1.85-1.65 (1H, m), 1.65 (6H, d, J=7.0 Hz), 0.78-0.50
(4H, m). Appearance: oily product.
EXAMPLE 441
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-octanesulfonate (Compound No. 2066)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.15-7.07 (2H, m), 6.89-6.85 (1H, s), 3.60-3.50 (2H, m), 2.15 (3H,
s), 2.15-1.98 (2H, m), 1.83-1.67 (1H, m), 1.58-1.15 (1OH, m),
0.95-0.83 (3H, m), 0.80-0.68 (2H, m), 0.65-0.55 (2H, m).
Appearance: paste state.
EXAMPLE 442
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
chloromethanesulfonate (Compound No. 2072)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.18-7.09 (2H, m), 6.92-6.85 (1H, m), 5.02 (2H, s), 2.16 (3H, s),
1.83-1.68 (1H, m), 0.80-0.68 (2H, m), 0.65-0.55 (2H, m).
Appearance: paste state.
EXAMPLE 443
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,2,2-trifluoroethanesulfonate (Compound No. 2136)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.55 (1H, s),
7.19-7.05 (2H, m), 6.90 (1H, dd, J=6.6, 2.9 Hz), 4.39 (2H, q, J=8.2
Hz), 2.15 (3H, s), 1.80-1.65 (1H, m), 0.80-0.50 (4H, m).
Appearance: amorphous.
EXAMPLE 444
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-chlorobenzenesulfonate (Compound No. 2212)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.01-7.92 (2H, m),
7.62-7.53 (3H, m), 7.13-7.00 (2H, m), 6.85-6.77 (1H, m), 2.04 (3H,
s), 1.58-1.45 (1H, m), 0.70-0.45 (4H, m). Appearance: gum
state.
EXAMPLE 445
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-nitrobenzenesulfonate (Compound No. 2300)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.50-8.39 (2H, m),
8.33-8.20 (2H, m), 7.59 (1H, s), 7.15-7.00 (2H, m), 6.85-6.75 (1H,
m), 1.94 (3H, s), 1.65-1.45 (1H, m), 0.75-0.45 (4H, m). Appearance:
gum state.
EXAMPLE 446
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methoxybenzenesulfonate (Compound No. 2309)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.99-7.91 (2H, m),
7.61 (1H, s), 7.11-6.98 (4H, m), 6.80 (1H, dd, J=2.6 Hz, 6.6 Hz),
3.90 (3H, s), 1.95 (3H, s), 1.60-1.45 (1H, m), 0.70-0.45 (4H, m).
Appearance: caramel-like.
EXAMPLE 447
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,4,6-trimethylbenzenesulfonate (Compound No. 2315)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (1H, s),
7.13-6.98 (4H, m), 6.85-6.75 (1H, m), 2.70 (6H, s), 2.32 (3H, s),
2.04 (3H, s), 1.65-1.45 (1H, m), 0.78-0.44 (4H, m). Appearance:
amorphous.
EXAMPLE 448
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,4,6-triisopropylbenzenesulfonate (Compound No. 2321)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.52 (1H, s),
7.28-7.20 (2H, m), 7.10-6.98 (2H, m), 6.85-6.75 (1H, m), 4.16 (2H,
septet, J=6.6 Hz), 2.93 (1H, septet, J=6.6 Hz), 1.93 (3H, s),
1.75-1.50 (1H, m), 1.35-1.20 (18H, m), 0.75-0.45 (4H, m).
Appearance: amorphous.
EXAMPLE 449
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H -pyrazol-5-yl
1,2-benzenedisulfonate (Compound No. 2327)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.52-8.40 (1H, m),
8.15-8.07 (1H, m), 8.00-7.82 (2H, m), 7.63 (1H, s), 7.18 (2H, s),
7.15-6.97 (3H, m), 6.79 (1H, dd, J=7.0, 2.6 Hz), 3.84 (3H, s), 2.11
(3H, s), 1.99 (3H, s), 1.75-1.57 (1H, m), 0.74-0.45 (4H, m).
Appearance: caramel-like.
EXAMPLE 450
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-chloro-3-nitrobenzenesulfonate (Compound No. 3786)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.55 (1H, d, J=2.2
Hz), 8.18 (1H, dd, J=8.8, 2.2 Hz), 7.81 (1H, d, J=8.8 Hz), 7.59
(1H, s), 7.13-7.06 (2H, m), 6.84-6.79 (1H, m), 1.98 (3H, s),
1.61-1.48 (1H, m), 0.68-0.52 (4H, m). Appearance: amorphous.
EXAMPLE 451
6-Chloro-3-[2-(2-chloro-2-fluorocyclopropyl)phenoxy]-4-pyridazinol
(Compound No. 2519)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.42-7.15 (4H, m),
6.70 (1H, s), 2.80-2.62 (1H, m), 2.18-1.65 (2H, m). Melting point
(.degree. C.): 175-177.
EXAMPLE 452
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,5-dichlorobenzenesulfonate (Compound No. 3780)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.09-8.08 (1H, m),
7.61-7.52 (3H, m), 7.12-7.01 (2H, m), 6.81-6.76 (1H, m), 1.98 (3H,
s), 1.67-1.49 (1H, m), 0.82-0.60 (2H, m), 0.58-0.48 (2H, m).
Appearance: amorphous.
EXAMPLE 453
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
10H-phenothiazine-10-carboxylate (Compound No. 3720)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.76-7.67 (3H, m),
7.49-7.40 (3H, m), 7.40-7.23 (3H, m), 7.20-7.10 (2H, m), 6.95-6.83
(1H, m), 2.19 (3H, s), 1.88-1.70 (1H, m), 0.85-0.57 (4H, m).
Appearance: amorphous.
EXAMPLE 454
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
9H-carbazole-9-carboxylate (Compound No. 3714)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.40 (2H, d, J=7.4
Hz), 8.02 (2H, d, J=7.0 Hz), 7.99 (1H, s), 7.60-7.35 (4H, m),
7.13-7.03 (2H, m), 6.92-6.80 (1H, m), 2.19 (3H, s), 1.90-1.73 (1H,
m), 0.84-0.50 (4H, m). Melting point (.degree. C.): 157-159.
EXAMPLE 455
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,4-dihydro-2(1H)-isoquinolinecarboxylate (Compound No. 3708)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (1H, s),
7.32-7.02 (6H, m), 6.90-6.78 (1H, m), 4.86 (1H, s), 4.72 (1H, s),
3.92 (1H, t, J=5.9 Hz), 3.81 (1H, t, J=5.9 Hz), 3.05-2.95 (2H, m),
2.14 (3H, s), 1.86-1.67 (1H, m), 0.80-0.50 (4H, m). Appearance:
caramel-like.
EXAMPLE 456
3-[3-(Benzyloxy)phenoxy]-6-chloro-4-pyridazinol (Compound No.
2547)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.48-7.25 (6H, m),
6.94-6.66 (4H, m), 5.07 (2H, s). Melting point (.degree. C.):
184-185.
EXAMPLE 457
3-[4-(Benzyloxy)phenoxy]-6-chloro-4-pyridazinol (Compound No.
2548)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.48-7.28 (5H, m),
7.12-6.96 (4H, m), 6.58 (1H, s), 5.07 (2H, s). Melting point
(.degree. C.): 170-180.
EXAMPLE 458
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-thiomorpholinecarboxylate (Compound No. 3702)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.53 (1H, s),
7.15-7.04 (2H, m), 6.92-6.80 (1H, m), 4.05-3.78 (4H, m), 2.75-2.64
(4H, m), 2.13 (3H, s), 1.85-1.65 (1H, m), 0.80-0.54 (4H, m).
Appearance: caramel-like.
EXAMPLE 459
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,6-dimethyl-4-morpholinecarboxylate (Compound No. 3696)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.54 (1H, s),
7.18-7.05 (2H, m), 6.94-6.80 (1H, m), 4.17-3.97 (2H, m), 3.78-3.55
(2H, m), 2.95-2.60 (2H, m), 2.14 (3H, s), 1.85-1.67 (1H, m),
1.35-1.15 (6H, m), 0.80-0.54 (4H, m). Appearance: caramel-like.
EXAMPLE 460
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-morpholinecarboxylate (Compound No. 3690)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.13-7.06 (2H, m), 6.90-6.83 (1H, m), 3.70-3.55 (8H, m), 2.14 (3H,
s), 1.83-1.68 (1H, m), 0.80-0.65 (2H, m), 0.65-0.53 (2H, m).
Melting point (.degree. C.): 102.5-103.5.
EXAMPLE 461
6-Chloro-3-[(1-methyl-1H-indol-4-yl)oxy]-4-pyridazinol (Compound
No. 2565)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.29 (1H, d, J=8.4
Hz), 7.17 (1H, t, J=7.7 Hz), 7.13 (1H, d, J=2.9 Hz), 6.85 (1H, d,
J=7.7 Hz), 6.72 (1H, s), 6.23 (1H, d, J=2.9 Hz), 4.87 (3H, s).
Melting point (.degree. C.): 203-206.
EXAMPLE 462
6-Chloro-3-[(1-methyl-1H-indol-7-yl)oxy]-4-pyridazinol (Compound
No. 2568)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.42 (1H, d, J=7.0
Hz), 7.07 (1H, d, J=2.9 Hz), 6.99 (1H, t, J=7.7 Hz), 6.86 (1H, d,
J=6,6 Hz), 6.74 (1H, s), 6.44 (1H, d, J=2.9 Hz), 3.80 (3H, s).
Melting point (.degree. C.): 219-221.
EXAMPLE 463
1-{4-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-3-methylphenyl}ethanone
(Compound No. 2570)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.94-7.86 (2H, m),
7.21-7.16 (1H, m), 6.75 (1H, s), 2.60 (3H, s), 2.25 (3H, s).
Melting point (.degree. C.): 182-184.
EXAMPLE 464
1-{4-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-3-methylphenyl}ethanone
O-methyloxime (Compound No. 2571)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.59-7.51 (2H, m),
7.11-7.06 (1H, m), 6.71 (1H, s), 3.95 (3H, s), 2.20 (3H, s).
Melting point (.degree. C.): 189-192.
EXAMPLE 465
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-phenyl-1-piperazinecarboxylate (Compound No. 3684)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.60 (1H, s),
7.35-7.23 (2H, m), 7.13-7.04 (2H, m), 7.00-6.80 (4H, m), 3.95-3.84
(2H, m), 3.84-3.72 (2H, m), 3.31-3.18 (4H, m), 2.15 (3H, s),
1.86-1.66 (1H, m), 0.80-0.53 (4H, m). Appearance: caramel-like.
EXAMPLE 466
4-{[4-(Benzoyloxy)-6-chloro-3-pyridazinyl]oxy}-3-methylphenyl
benzoate (Compound No. 3850)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.21-8.17 (4H, m),
7.72-7.48 (7H, m), 7.22-7.07 (3H, m), 2.21 (3H, s). Melting point
(.degree. C.): 118-120.
EXAMPLE 467
Methyl 3-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]-4-methoxybenzoate
(Compound No. 2574)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.95 (1H, dd J=8.6,
2.2 Hz), 7.78 (1H, d, J=1.8 Hz), 7.19 (1H, d, J=8.8 Hz), 6.71 (1H,
s), 3.87 (3H, s), 3.84 (3H, s). Melting point (.degree. C.):
115-123.
EXAMPLE 468
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methyl-1-piperazinecarboxylate (Compound No. 3678)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (1H, s),
7.15-7.04 (2H, m), 6.90-6.80 (1H, m), 3.80-3.55 (4H, m), 2.54-2.40
(4H, m), 2.32 (3H, s), 2.14 (3H, s), 1.85-1.67 (1H, m), 0.80-0.52
(4H, m). Appearance: caramel-like.
EXAMPLE 469
6-Chloro-3-(2-isopropenyl-6-methylphenoxy)-4-pyridazinol (Compound
No. 2577)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.20-7.10 (3H, m),
6.66 (1H, s), 5.01 (1H, m), 4.95 (1H, m), 2.15 (3H, s), 1.99 (3H,
s). Melting point (.degree. C.): 183-186.
EXAMPLE 470
6-Chloro-3-[(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)oxy-4-pyridazinol
(Compound No. 2585)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.15 (1H, d, J=8.1
Hz), 6.95 (2H, br.d, J=8.1 Hz), 6.68 (1H, s), 2.89 (2H, t, J=7.3
Hz), 1.96 (2H, t, J=7.3 Hz), 1.27 (6H, s). Melting point (.degree.
C.): 209-212.
EXAMPLE 471
3-(3-Bromo-6-cyclopropyl-2-methylphenoxy)-6-chloro-4-pyridazinol
(Compound No. 2587)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.38 (1H, d, J=8.4
Hz), 6.78 (1H, d, J=8.4 Hz), 6.72 (1H, s), 2.22 (3H, s), 1.85-1.72
(1H, m), 0.85-0.72 (2H, m), 0.65-0.50 (2H, m). Melting point
(.degree. C.): 234-235.
EXAMPLE 472
6-Chloro-3-(6-cyclopropyl-2-methyl-3-nitrophenoxy)-4-pyridazinol
(Compound No. 2589)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.80 (1H, d, J=8.4
Hz), 7.02 (1H, d, J=8.4 Hz), 6.77 (1H, s), 2.32 (3H, s), 1.99-1.88
(1H, m), 0.95-0.88 (2H, m), 0.74-0.70 (2H, m). Melting point
(.degree. C.): 140-143.
EXAMPLE 473
6-Chloro-3-[(5-methyl-1,3-dihydro-2-benzofuran-4-yl)oxy]-4-pyridazinol
(Compound No. 2592)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.20 (1H, d, J=7.7
Hz), 7.08 (1H, d, J=7.7 Hz), 5.06 (2H, br.s), 4.88 (2H, br.s), 2.16
(3H, s). Melting point (.degree. C.): 188-200.
EXAMPLE 474
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,2,6,6-tetramethyl-1-piperidinecarboxylate (Compound No. 3672)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7,53 (1H, s),
7.14-7.03 (2H, m), 6.90-6.78 (1H, m), 2.13 (3H, s), 1.90-1.62 (7H,
m), 1.55 (12H, s), 0.80-0.52 (4H, m). Appearance: caramel-like.
EXAMPLE 475
6-Chloro-3-(2-fluoro-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 2597)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.92 (1H, d, J=7.0
Hz), 6.73 (1H, s), 2.24 (3H, s), 2.21 (3H, s), 2.06 (3H, s).
Melting point (.degree. C.): 258-260.
EXAMPLE 476
6-Chloro-3-(2-chloro-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 2599)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 7.11 (1H, s), 6.86
(1H, br.s), 2.29 (3H, s), 2.24 (3H, s), 1.99 (3H, s). Melting point
(.degree. C.): 298-300.
EXAMPLE 477
6-Chloro-3-(2-iodo-3,5,6-trimethylphenoxy)-4-pyridazinol (Compound
No. 2600)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.06 (1H, s), 6.75
(1H, s) 2.40 (3H, s), 2.26 (3H, s), 2.09 (3H, s). Melting point
(.degree. C.): 235 (decomposed).
EXAMPLE 478
6-Chloro-3-(2-ethyl-3,5,6-trimethylphenoxy)-4-pyridazinol (Compound
No. 2601)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 6.95 (1H, s), 6.81
(1H, br.s), 2.32 (2H, q, J=7.5 Hz), 2.24 (3H, s), 2.12 (3H, s),
1.94 (3H, s), 1.04 (3H, t, J=7.5 Hz). Melting point (.degree. C.):
188-195.
EXAMPLE 479
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1,4-dioxa-8-azaspiro[4.5]decan-8-carboxylate (Compound No.
3666)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.15-7.04 (2H, m), 6.92-6.80 (1H, m), 3.99 (4H, s), 3.85-3.62 (4H,
m), 2.14 (3H, s), 1.85-1.65 (5H, m), 0.80-0.50 (4H, m). Appearance:
caramel-like.
EXAMPLE 480
6-Chloro-3-(2-isopropenyl-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 2605)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.91 (1H, s), 6.58
(1H, s), 5.00-4.90 (2H, bm), 2.27 (3H, s), 2.20 (3H, s), 2.07 (3H,
s), 1.96 (3H, s). Appearance: amorphous.
EXAMPLE 481
1-[6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
4-ethyl 1,4-piperidinedicarboxylate (Compound No. 3660)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56 (1H, s)
7.13-7.04 (2H, m), 6.90-6.80 (1H, m), 4.30-4.00 (2H, m), 3.35-3.02
(2H, m), 2.65-2.45 (1H, m), 2.14 (3H, s), 2.10-1.93 (3H, m),
1.93-1.65 (4H, m), 1.25 (3H, t, J=7.0 Hz), 0.80-0.54 (4H, m).
Appearance: caramel-like.
EXAMPLE 482
1-{2-[(6-Chloro-4-hydroxy3-pyridazinyl)oxy]-3,4,6-trimethylphenyl}ethanone
(Compound No. 2607)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.55 (1H, s), 6.72
(1H, s) 2.45 (3H, s), 2.36 (3H, s), 2.29 (3H, s), 2.11 (3H, s).
Appearance: amorphous.
EXAMPLE 483
6-Chloro-3-(2,3,5-trimethyl-6-nitrophenoxy)-4-pyridazinol (Compound
No. 2608)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.11 (1H, s), 6.65
(1H, s), 2.33 (3H, s), 2.28 (3H, s), 2.05 (3H, s). Melting point
(.degree. C.): 172-174.
EXAMPLE 484
6-Chloro-3-(2,4-dichloro-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 2609)
.sup.1H-NMR (200 MHz, DMSO-d.sub.6) .delta. ppm: 6.91 (1H, s), 2.46
(3H, s), 2.36 (3H, s), 2.10 (3H, s).
EXAMPLE 485
6-Chloro-3-(2,3,4,5,6-pentamethylphenoxy)-4-pyridazinol (Compound
No. 2614)
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.69 (1H, s), 2.23
(3H, s), 2.21 (6H, s), 2.02 (6H, s). Melting point (.degree. C.):
238-240 (decomposed).
EXAMPLE 486
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,3-dimethylbutanoate (Compound No. 2662)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.37 (1H, s),
7.13-7.05 (2H, s), 6.88-6.82 (1H, s), 2.55 (2H, s), 2.12 (3H, s),
1.82-1.67 (1H, m), 1.15 (9H, s), 0.80-0.65 (2H, m), 0.63-0.52 (2H,
m). Melting point (.degree. C.): 91-92.
EXAMPLE 487
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-adamantanecarboxylate (Compound No. 2671)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.37 (1H, s),
7.12-7.05 (2H, m), 6.92-6.80 (1H, m), 2.13 (3H, s), 2.08 (9H, s),
1.76 (7H, br.s), 0.85-0.45 (4H, m). Appearance: oily product.
EXAMPLE 488
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-methylacrylate (Compound No. 2677)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.48 (1H, s),
7.14-7.05 (2H, m), 6.89-6.83 (1H, m), 6.46 (1H, br.s), 5.91 (1H,
br.s), 2.13 (3H, s), 2.09 (3H, s), 1.81-1.68 (1H, m), 0.78-0.53
(4H, m). Melting point (.degree. C.): 98-100.
EXAMPLE 489
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-bromo-2-methylpropanoate (Compound No. 2697)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.47 (1H, s),
7.11-7.08 (2H, m), 6.89-6.85 (1H, m), 2.13 (3H, s), 2.10 (6H, s),
1.77-1.69 (1H, m), 0.74-0.58 (4H, m). Melting point (.degree. C.):
69-71.
EXAMPLE 490
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-chloro-2,2-dimethylpropanoate (Compound No. 2703)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.43 (1H, s),
7.13-7.05 (2H, m), 6.90-6.84 (1H, m), 3.76 (2H, s), 2.13 (3H, s),
1.83-1.65 (1H, m), 1.50 (6H, s), 0.85-0.45 (4H, br.s). Melting
point (.degree. C.): 112-115.
EXAMPLE 491
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-bromopentanoate (Compound No. 2709)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.83 (1H, s),
7.11-7.05 (2H, m), 6.86-6.82 (1H, m), 3.43 (2H, d, J=6.2 Hz), 2.73
(2H, d, J=7.0 Hz), 2.12 (3H, s), 2.04-1.93 (4H, m), 1.77-1.69 (1H,
m), 0.74-0.56 (4H, m). Appearance: caramel-like.
EXAMPLE 492
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
hydratropate (Compound No. 2715)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.42-7.20 (5H, m),
7.32 (1H, s), 7.15-7.02 (2H, m), 6.86-6.75 (1H, m), 4.20-4.00 (1H,
m), 2.04 (3H, s), 1.66 (3H, d, J=7.0 Hz), 1.70-1.50 (1H, m),
0.70-0.42 (4H, m). Appearance: oily product.
EXAMPLE 493
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
(4-methoxyphenyl)acetate (Compound No. 2721)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.37 (1H, s), 7.27
(2H, d, J=8.2 Hz), 7.13-7.05 (2H, m), 6.89-6.80 (3H, m), 3.91 (2H,
s), 3.76 (3H, s), 2.07 (3H, s), 1.73-1.60 (1H, m), 0.75-0.50 (4H,
m). Appearance: paste state.
EXAMPLE 494
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl ethyl
succinate (Compound No. 2727)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.08-6.92 (2H, m),
6.85-6.68 (1H, m), 6.55 (1H, s), 4.14 (2H, br.q, J=7.1 Hz), 3.00
(1H, t, J=7.0 Hz), 2.76 (1H, t, J=7.0 Hz), 2.61 (2H, br.s), 1.98
(3H, s), 1.78-1.60 (1H, m), 1.25 (3H, t, J=7.1 Hz), 0.75-0.40 (4H,
m). Appearance: amorphous.
EXAMPLE 495
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methyl-1-piperidinecarboxylate (Compound No. 3654)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56 (1H, s),
7.14-7.04 (2H, m), 6.90-6.80 (1H, m), 4.35-4.10 (2H, m), 3.15-2.80
(2H, m), 2.14 (3H, s), 1.85-1.50 (4H, m), 1.35-1.06 (2H, m), 0.96
(3H, d, J=6.2 Hz), 0.80-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 496
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-bromo-1-piperidinecarboxylate (Compound No. 3648)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.55 (1H, s),
7.15-7.04 (2H, m), 6.90-6.80 (1H, m), 4.54-4.38 (1H, m), 4.00-3.53
(4H, m), 2.30-1.90 (7H, m), 1.85-1.67 (1H, m), 0.80-0.50 (4H, m).
Appearance: caramel-like.
EXAMPLE 497
Bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
succinate (Compound No. 2733)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.32 (2H, s),
7.14-7.03 (4H, m), 6.88-6.81 (2H, m), 3.17 (4H, s), 2.10 (6H, s),
1.80-1.65 (2H, m), 0.78-0.53 (8H, m). Appearance: caramel-like.
EXAMPLE 498
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
methoxyacetate (Compound No. 2752)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.43 (1H, s),
7.15-7.04 (2H, m), 6.90-6.82 (1H, m), 4.41 (2H, s), 3.55 (3H, s),
2.12 (3H, s), 1.82-1.67 (1H, m), 0.80-0.67 (2H, m), 0.64-0.55 (2H,
m). Appearance: paste state.
EXAMPLE 499
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
phenoxyacetate (Compound No. 2758)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.42 (1H, s),
7.29-7.25 (2H, m), 7.23-6.96 (5H, m), 6.89-6.83 (1H, m), 5.00 (2H,
s), 2.08 (3H, s), 1.73-1.64 (1H, m), 0.71-0.54 (4H, m). Appearance:
caramel-like.
EXAMPLE 500
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-phenoxypropanoate (Compound No. 2764)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.33 (1H, s),
7.25-7.19 (2H, m), 7.17-7.04 (2H, m), 7.00-6.91 (3H, m), 6.86-6.82
(1H, m), 5.09 (1H, q, J=6.6 Hz), 2.05 (3H, s), 1.84 (3H, d, J=6.6
Hz), 1.64-1.58 (1H, m), 0.68-0.52 (4H, m). Appearance:
caramel-like.
EXAMPLE 501
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
methoxy(phenyl)acetate (Compound No. 2770)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56-7.51 (2H, m),
7.40-7.30 (4H, m), 7.12-7.02 (2H, m), 6.83-6.78 (1H, m), 5.10 (1H,
s), 3.52 (3H, s), 2.01 (3H, s), 1.67-1.50 (1H, m), 0.70-0.43 (4H,
m). Appearance: paste state.
EXAMPLE 502
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-(methylsulfanyl)propanoate (Compound No. 2776)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.42 (1H, s),
7.10-7.00 (2H, m), 6.90-6.77 (1H, m), 3.07-2.83 (4H, m), 2.17 (3H,
s), 2.12 (3H, s), 1.85-1.65 (1H, m), 0.80-0.50 (4H, m). Appearance:
caramel-like.
EXAMPLE 503
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
oxo(2-thienyl)acetate (Compound No. 2782)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.07 (1H, dd, J=1.5
Hz, 4.1 Hz), 7.77 (1H, dd, J=1.5 Hz, 4.1 Hz), 7.58 (1H, s), 7.22
(1H, t, J=4.0 Hz), 7.10-7.02 (2H, m), 6.90-6.77 (1H, m), 2.15 (3H,
s), 1.90-1.70 (1H, m), 0.85-0.50 (4H, m). Appearance:
caramel-like.
EXAMPLE 504
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-fluorobenzoate (Compound No. 2788)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.17-8.09 (1H, m),
7.73-7.62 (1H, m), 7.57 (1H, s), 7.36-7.20 (2H, m), 7.09-7.07 (2H,
m), 6.87-6.82 (1H, m), 2.16 (3H, s), 1.85-1.72 (1H, m), 0.76-0.56
(4H, m). Appearance: amorphous.
EXAMPLE 505
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-bromobenzoate (Compound No. 2805)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.20-8.05 (1H, m),
7.85-7.70 (1H, m), 7.59 (1H, s), 7.55-7.38 (2H, m), 7.15-7.00 (2H,
m), 6.90-6.80 (1H, m), 2.17 (3H, s), 1.88-1.70 (1H, m), 0.80-0.50
(4H, m). Appearance: caramel-like.
EXAMPLE 506
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-iodobenzoate (Compound No. 2814)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.20-8.05 (2H, m),
7.60-7.44 (2H, m), 7.35-7.20 (1H, m), 7.13-7.00 (2H, m), 6.90-6.78
(1H, m), 2.17 (3H, s), 1.90-1.72 (1H, m), 0.85-0.50 (4H, m).
Appearance: caramel-like.
EXAMPLE 507
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-(trifluoromethyl)benzoate (Compound No. 2820)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.13-8.09 (1H, m),
7.91-7.86 (1H, m), 7.76-7.72 (2H, m), 7.55 (1H, s), 7.11-7.06 (2H,
m), 6.88-6.83 (1H, m), 2.16 (3H, s), 1.86-1.71 (1H, m), 0.75-0.56
(4H, m). Appearance: caramel-like.
EXAMPLE 508
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-benzylbenzoate (Compound No. 2826)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.22-8.18 (1H, d,
J=7.2 Hz) 7.62-7.54 (1H, t, J=7.6 Hz), 7.44-7.06 (1OH, m),
6.85-6.81 (1H, m), 4.46 (1H, s), 2.11 (3H, s), 1.80-1.67 (1H, m),
0.75-0.64 (2H, m), 0.60-0.52 (2H, m). Appearance: paste state.
EXAMPLE 509
Bis[6-chloro-3-(2-methylphenoxy)-4-pyridazinyl] phthalate (Compound
No. 2827)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.06 (2H, dd, J=6.0,
3.4 Hz) 7.57 (2H, s), 7.25-7.15 (8H, m), 7.05-7.01 (2H, m), 2.14
(6H, s). Melting point (.degree. C.): 157-158.
EXAMPLE 510
1-[6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
2-methyl 1,2-piperidinedicarboxylate (Compound No. 3642)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.60 (0.5H, s), 7.59
(0.5H, s), 7.14-7.03 (2H, m), 6.92-6.80 (1H, m), 5.10-4.90 (1H, m),
4.32-4.06 (1H, m), 3.73 (1.5H, s), 3.71 (1.5H, s), 3.40-3.05 (1H,
m), 2.43-2.20 (1H, m), 2.15 (1.5H, s), 2.13 (1.5H, s), 2.00-1.20
(6H, m), 0.80-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 511
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-nitrobenzoate (Compound No. 2850)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.15-8.05 (1H, m),
7.95-7.72 (3H, m), 7.65 (1H, s), 7.14-7.05 (2H, m), 6.90-6.80 (1H,
m), 2.15 (3H, s), 1.85-1.70 (1H, m), 0.78-0.65 (2H, m), 0.65-0.50
(2H, m). Appearance: oily product.
EXAMPLE 512
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-phenoxybenzoate (Compound No. 2856)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.35 (1H, dd, J=8.2,
1.8 Hz), 8.15 (1H, dd, J=8.0, 1.8 Hz), 7.74 (1H, dt, J=7.0, 1.4
Hz), 7.61-7.21 (5H, m), 7.15-6.98 (4H, m), 6.84-6.79 (1H, m), 2.09
(3H, s), 1.80-1.68 (1H, m), 0.70-0.71 (2H, m), 0.59-0.51 (2H, m).
Appearance: paste state.
EXAMPLE 513
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-chlorobenzoate (Compound No. 2868)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.18 (1H, d, J=1.8
Hz), 8.10 (1H, d, J=8.1 Hz), 7.68 (1H, br.d, J=9.2 Hz), 7.57 (1H,
s), 7.50 (1H, t, J=8.1 Hz), 7.08 (1H, d, J=5.8 Hz), 7.07 (1H, d,
J=3.7 Hz), 6.85 (1H, dd, J=5.8, 3.7 Hz), 2.15 (3H, s), 1.85-1.66
(1H, m), 0.80-0.50 (4H, m). Appearance: amorphous.
EXAMPLE 514
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-fluorobenzoate (Compound No. 2862)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.02 (1H, dd, J=6.2,
1.5 Hz), 7.89 (1H, br.d, J=8.8 Hz), 7.60-7.34 (2H, m), 7.59 (1H,
s), 7.13-7.04 (2H, m), 6.90-6.78 (1H, m), 2.15 (3H, s), 1.83-1.68
(1H, m), 0.80-0.50 (4H, m). Appearance: oily product.
EXAMPLE 515
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-bromobenzoate (Compound No. 2874)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.33 (1H, s), 8.14
(1H, d, J=8.0 Hz), 7.82 (1H, d, J=8.0 Hz), 7.56 (1H, s), 7.43 (1H,
t, J=8.0 Hz), 7.13-7.03 (2H, m), 6.90-6.80 (1H, m), 2.15 (3H, s),
1.85-1.68 (1H, m), 0.80-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 516
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-iodobenzoate (Compound No. 2880)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.54 (1H, d, J=1.8
Hz), 8.20-8.15 (1H, m), 8.03 (1H, d, J=8.1 Hz), 7.56 (1H, s),
7.34-7.26 (1H, m), 7.13-7.05 (2H, m), 6.89-6.82 (1H, m), 2.15 (3H,
s), 1.83-1.71 (1H, m), 0.80-0.68 (2H, m), 0.65-0.52 (2H, m).
Appearance: amorphous.
EXAMPLE 517
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-(trifluoromethyl)benzoate (Compound No. 2900)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.47 (1H, s), 8.41
(1H, d, J=7.7 Hz), 7.96 (1H, d, J=7.3 Hz), 7.75-7.67 (1H, m), 7.58
(1H, s), 7.12-7.06 (2H, m), 6.89-6.82 (1H, m), 2.16 (3H, s),
1.84-1.71 (1H, m), 0.80-0.53 (4H, m). Appearance: caramel-like.
EXAMPLE 518
Bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
isophthalate (Compound No. 2906)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.02 (1H, s), 8.53
(2H, d, J=8.2 Hz), 7.78 (1H, t, J=7.8 Hz), 7.58 (2H, s), 7.08-7.06
(4H, m), 6.86-6.82 (2H, m), 2.14 (6H, s), 1.83-1.68 (2H, m),
0.78-0.69 (4H, m), 0.60-0.53 (4H, m). Appearance: paste state.
EXAMPLE 519
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-nitrobenzoate (Compound No. 2918)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.05-9.04 (1H, m),
8.59-8.52 (2H, m), 7.79 (1H, t, J=7.7 Hz), 7.59 (1H, s), 7.13-7.07
(2H, m), 6.89-6.82 (1H, m), 2.15 (3H, s), 1.83-1.72 (1H, m),
0.80-0.54 (4H, m). Appearance: caramel-like.
EXAMPLE 520
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-phenoxybenzoate (Compound No. 2924)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.95-7.90 (1H, m),
7.80-7.78 (1H, m), 7.57 (1H, s), 7.50 (1H, t, J=8.0 Hz), 7.40-7.30
(3H, m), 7.17-7.10 (1H, m), 7.09-7.03 (3H, m), 7.07 (1H, s),
6.87-6.82 (1H, m), 2.13 (3H, s), 1.81-1.67 (1H, m), 0.78-0.66 (2H,
m). 0.59-0.54 (2H, m). Appearance: paste state.
EXAMPLE 521
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-fluorobenzoate (Compound No. 2930)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.30-8.18 (2H, m),
7.59 (1H, s), 7.30-7.15 (2H, m), 7.15-7.02 (2H, m), 6.90-6.78 (1H,
m), 2.15 (3H, s), 1.85-1.70 (1H, m), 0.80-0.50 (4H, m). Appearance:
caramel-like.
EXAMPLE 522
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-ethylbenzoate (Compound No. 2961)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.13 (2H, d, J=8.5
Hz), 7.60 (1H, s), 7.36 (2H, d, J=8.5 Hz), 7.12-7.04 (2H, m),
6.88-6.81 (1H, m), 2.75 (2H, q, J=7.6 Hz), 2.04 (3H, s), 1.85-1.71
(1H, m), 1.28 (3H, t, J=7.6 Hz), 0.79-0.65 (2H, m), 0.61-0.52 (2H,
m) Appearance: paste state.
EXAMPLE 523
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-propylbenzoate (Compound No. 2970)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.12 (2H, d, J=8.4
Hz), 7.59 (1H, s), 7.34 (2H, d, J=8.4 Hz), 7.12-7.05 (2H, m),
6.88-6.81 (1H, m), 2.69 (2H, t, J=7.3 Hz), 2.16 (3H, s), 1.85-1.60
(3H, m), 0.96 (3H, t, J=7.3 Hz), 0.80-0.68 (2H, m), 0.63-0.52 (2H,
m). Appearance: paste state.
EXAMPLE 524
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-isopropylbenzoate (Compound No. 2976)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.14 (2H, d, J=8.4
Hz), 7.59 (1H, s), 7.40 (2H, d, J=8.4 Hz), 7.12-7.05 (2H, m),
6.90-6.82 (1H, m), 3.01 (1H, septet, J=7.0 Hz), 2.15 (3H, s),
1.85-1.70 (1H, m), 1.29 (6H, d, J=7.0 Hz), 0.80-0.65 (2H, m),
0.63-0.52 (2H, m). Appearance: paste state.
EXAMPLE 525
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-butylbenzoate (Compound No. 2982)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.12 (2H, d, J=8.1
Hz), 7.59 (1H, s), 7.35 (2H, d, J=8.1 Hz), 7.12-7.03 (2H, m),
6.89-6.81 (1H, m), 2.72 (2H, t, J=7.3 Hz), 2.16 (3H, s), 1.85-1.57
(3H, m), 1.47-1.22 (2H, m), 0.94 (3H, t, J=7.3 Hz), 0.80-0.68 (2H,
m), 0.65-0.55 (2H, m). Appearance: paste state.
EXAMPLE 526
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(trifluoromethyl)benzoate (Compound No. 2988)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.34 (2H, d, J=8.8
Hz), 7.83 (2H, d, J=8.8 Hz), 7.60 (1H, s), 7.14-7.07 (2H, m),
6.89-6.83 (1H, m), 2.15 (3H, s), 1.83-1.72 (1H, m), 0.79-0.71 (2H,
m), 0.63-0.54 (2H, m). Melting point (.degree. C.): 127-128.
EXAMPLE 527
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-cyanobenzoate (Compound No. 2994)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.33 (2H, d, J=8.8
Hz), 7.86 (2H, d, J=8.8 Hz), 7.60 (1H, s), 7.14-7.07 (2H, m),
6.89-6.83 (1H, m), 2.14. (3H, s), 1.82-1.68 (1H, m), 0.79-0.53 (4H,
m). Appearance: caramel-like.
EXAMPLE 528
Bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
terephthalate (Compound No. 3001)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.39 (4H, s), 7.62
(2H, s) 7.10-7.07 (4H, m), 6.87-6.83 (2H, m), 2.15 (6H, s),
1.81-1.68 (2H, m), 0.78-0.70 (4H, m), 0.61-0.53 (4H, m). Melting
point (.degree. C.): 247-249.
EXAMPLE 529
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
[1,1'-biphenyl]-4-carboxylate (Compound No. 3016)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.31-8.23 (2H, m),
7.79-7.74 (2H, m), 7.67-7.62 (3H, m), 7.54-7.42 (3H, m), 7.09-7.06
(2H, m), 6.87-6.82 (1H, m), 2.17 (3H, s), 1.84-1.75 (1H, m),
0.77-0.56 (4H, m). Melting point (.degree. C.): 135-137.
EXAMPLE 530
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(trifluoromethoxy)benzoate (Compound No. 3022)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.28 (2H, d, J=9.2
Hz), 7.59 (1H, s), 7.38 (2H, d, J=9.2 Hz), 7.14-7.04 (2H, m),
6.89-6.82 (1H, m), 2.15 (3H, s), 1.83-1.69 (1H, m), 0.78-0.65 (2H,
m), 0.62-0.53 (2H, m) Appearance: paste state.
EXAMPLE 531
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(benzyloxy)benzoate (Compound No. 3028)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.16 (2H, d, J=9.2
Hz), 7.60 (1H, s), 7.50-7.30 (5H, m), 7.10-7.03 (4H, m), 6.89-6.82
(1H, m), 5.17 (2H, s), 2.15 (3H, s), 1.85-1.72 (1H, m), 0.80-0.68
(2H, m), 0.65-0.53 (2H, m). Appearance: paste state.
EXAMPLE 532
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,3-difluorobenzoate (Compound No. 3034)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.93-7.85 (1H, m),
7.57 (1H, s), 7.57-7.44 (1H, m), 7.32-7.21 (1H, m), 7.10-7.05 (2H,
m), 6.87-6.82 (1H, m), 2.15 (3H, s), 1.81-1.73 (1H, m), 0.76-0.72
(2H, m), 0.60-0.56 (2H, m). Appearance: paste state.
EXAMPLE 533
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-fluoro-3-(trifluoromethyl)benzoate (Compound No. 3040)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.36-8.28 (1H, m),
7.99-7.92 (1H, m), 7.56 (1H, s), 7.49-7.41 (1H, m), 7.13-7.05 (2H,
m), 6.89-6.83 (1H, m), 2.15 (3H, s), 1.84-1.72 (1H, m), 0.80-0.54
(4H, m). Appearance: amorphous.
EXAMPLE 534
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,3-dimethylbenzoate (Compound No. 3046)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.00-7.96 (1H, m),
7.54 (1H, s), 7.45-7.41 (1H, m), 7.27-7.20 (1H, m), 7.14-7.05 (2H,
m), 6.89-6.82 (1H, m), 2.57 (3H, s), 2.37 (3H, s), 2.16 (3H, s),
1.86-1.72 (1H, m), 0.79-0.69 (2H, m), 0.61-0.53 (2H, m).
Appearance: paste state.
EXAMPLE 535
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-chloro-2-methylbenzoate (Compound No. 3052)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.04 (1H, d, J=8.1
Hz), 7.65 (1H, d, J=8.1 Hz), 7.54 (1H, s), 7.33-7.25 (1H, m),
7.13-7.06 (2H, m), 6.89-6.83 (1H, m), 2.73 (3H, s), 2.15 (3H, s),
1.83-1.71 (1H, m), 0.79-0.68 (2H, m), 0.65-0.53 (2H, m).
Appearance: amorphous.
EXAMPLE 536
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,4-difluorobenzoate (Compound No. 3058)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.23-8.12 (1H, m),
7.56 (1H, s), 7.10-6.94 (4H, m), 6.87-6.82 (1H, m), 2.15 (3H, s),
1.81-1.73 (1H, m), 0.75-0.56 (4H, m). Appearance: amorphous.
EXAMPLE 537
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-chloro-2-fluorobenzoate (Compound No. 3064)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.07 (1H, dd, J=7.4
Hz, 8.5 Hz), 7.55 (1H, s), 7.38-7.22 (2H, m), 7.14-7.03 (2H, m),
6.90-6.78 (1H, m), 2.15 (3H, s), 1.85-1.68 (1H, m), 0.80-0.50 (4H,
m). Appearance: caramel-like.
EXAMPLE 538
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-fluoro-4-(trifluoromethyl)benzoate (Compound No. 3070)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.30-8.22 (1H, m),
7.61-7.52 (2H, m), 7.57 (1H, s), 7.14-7.05 (2H, m), 6.87-6.82 (1H,
m), 2.15 (3H, m), 1.83-1.69 (1H, m), 0.78-0.70 (2H, m), 0.65-0.55
(2H, m). Appearance: paste state.
EXAMPLE 539
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-chloro-4-fluorobenzoate (Compound No. 3076)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.25-8.18 (1H, m),
7.57 (1H, s), 7.34-7.29 (1H, m), 7.19-7.05 (3H, m), 6.89-6.82 (1H,
m), 2.15 (3H, m), 1.84-1.70 (1H, m), 0.79-0.68 (2H, m), 0.64-0.53
(2H, m). Appearance: paste state.
EXAMPLE 540
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-bromo-2-chlorobenzoate (Compound No. 3082)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.01 (1H, d, J=8.4
Hz), 7.76 (1H, d, J=1.8 Hz), 7.60-7.55 (2H, m), 7.10-7.07 (2H, m),
6.87-6.83 (1H, m), 2.15 (3H, s), 1.83-1.71 (1H, m), 0.77-0.71 (2H,
m), 0.62-0.56 (2H, m). Appearance: paste state.
EXAMPLE 541
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-bromo-2-methylbenzoate (Compound No. 3088)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.05 (1H, d, J=8.4
Hz), 7.56-7.48 (3H, m), 7.09-7.07 (2H, m), 6.86-6.82 (1H, m), 2.14
(3H, s), 2.04 (3H, s), 1.85-1.72 (1H, m), 0.79-0.71 (2H, m),
0.64-0.55 (2H, m). Appearance: paste state.
EXAMPLE 542
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,4-dimethylbenzoate (Compound No. 3094)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.11 (1H, d, J=8.9
Hz), 7.57 (1H, s), 7.16-7.13 (2H, m), 7.09-7.05 (2H, m), 6.88-6.81
(1H, m), 2.65 (3H, s), 2.41 (3H, s), 2.15 (3H, s), 1.85-1.71 (1H,
m), 0.80-0.68 (2H, m), 0.67-0.55 (2H, m). Appearance: paste
state.
EXAMPLE 543
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,5-dichlorobenzoate (Compound No. 3100)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.10 (1H, d, J=2.2
Hz), 7.60-7.45 (3H, m), 7.15-7.04 (2H, m), 6.90-6.78 (1H, m), 2.15
(3H, s), 1.85-1.70 (1H, m), 0.80-0.50 (4H, m). Melting point
(.degree. C.): 128-130.
EXAMPLE 544
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-bromo-2-chlorobenzoate (Compound No. 3106)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.20 (1H, d, J=2.2
Hz), 7.68 (1H, dd, J=2.2 Hz, 8.4 Hz), 7.54 (1H, s), 7.43 (1H, d,
J=8.4 Hz), 7.14-7.03 (2H, m), 6.92-6.80 (1H, m), 2.15 (3H, s),
1.87-1.70 (1H, m), 0.85-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 545
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-bromo-5-methoxybenzoate (Compound No. 3112)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.67-7.57 (3H, m),
7.12-7.00 (3H, m), 6.87-6.82 (1H, m), 3.85 (3H, s), 2.16 (3H, s),
1.87-1.75 (1H, m), 0.80-0.68 (2H, m), 0.65-0.55 (2H, m).
Appearance: paste state.
EXAMPLE 546
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,5-dimethylbenzoate (Compound No. 3129)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.99 (1H, s), 7.54
(1H, s) 7.37-7.30 (1H, m), 7.25-7.21 (1H, m), 7.13-7.05 (2H, m),
6.89-6.82 (1H, m), 2.63 (3H, s), 2.40 (3H, s), 2.16 (3H, s),
1.86-1.72 (1H, m), 0.80-0.70 (2H, m), 0.62-0.54 (2H, m).
Appearance: oily product.
EXAMPLE 547
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,6-difluorobenzoate (Compound No. 3138)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.68-7.50 (2H, m),
7.15-7.00 (4H, m), 6.90-6.77 (1H, m), 2.15 (3H, s), 1.90-1.70 (1H,
m), 0.85-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 548
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-chloro-6-fluorobenzoate (Compound No. 3144)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.57-7.00 (5H, m), 6.90-6.78 (1H, m), 2.16 (3H, s), 1.90-1.75 (1H,
m), 0.80-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 549
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,6-dichlorobenzoate (Compound No. 3150)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.43-7.41 (3H, m), 7.11-7.08 (2H, m), 6.88-6.83 (1H, m), 2.17 (3H,
s), 1.85-1.77 (1H, m), 0.74-0.56 (4H, m). Appearance:
amorphous.
EXAMPLE 550
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,6-dimethylbenzoate (Compound No. 3156)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.48 (1H, s), 7.32
(1H, dd, J=8.4, 7.0 Hz), 7.15-7.07 (3H, m), 6.87-6.83 (1H, m), 2.53
(6H, s), 2.16 (3H, s), 1.84-1.76 (1H, m), 0.75-0.69 (2H, m),
0.62-0.57 (2H, m). Appearance: paste state.
EXAMPLE 551
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,6-dimethoxybenzoate (Compound No. 3162)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (1H, s), 7.39
(1H, t, J=8.8 Hz), 7.09-7.07 (2H, m), 6.85-6.81 (1H, m), 6.62 (2H,
d, J=6.6 Hz), 3.84 (6H, s), 2.17 (3H, s), 1.96-1.81 (1H, m),
0.74-0.55 (4H, m). Melting point (.degree. C.): 127-128.
EXAMPLE 552
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,4-difluorobenzoate (Compound No. 3168)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.10-7.99 (2H, m),
7.58 (1H, s), 7.43-7.25 (1H, m), 7.15-7.02 (2H, m), 6.90-6.80 (1H,
m), 2.15 (3H, s), 1.83-1.67 (1H, m), 0.80-0.50 (4H, m). Appearance:
caramel-like.
EXAMPLE 553
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-fluoro-4-methylbenzoate (Compound No. 3185)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.90 (1H, d, J=8.1
Hz), 7.83 (1H, d, J=9.9 Hz), 7.59 (1H, s), 7.37 (1H, dd, J=7.3 Hz,
7.7 Hz), 7.15-7.00 (2H, m), 6.90-6.78 (1H, m), 2.39 (3H, d, 1.5
Hz), 2.15 (3H, s), 1.85-1.67 (1H, m), 0.80-0.50 (4H, m).
Appearance: caramel-like.
EXAMPLE 554
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,4-dichlorobenzoate (Compound No. 3194)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.29 (1H, d, J=1.8
Hz), 8.03 (1H, dd, J=8.4, 2.2 Hz), 7.65 (1H, d, J=8.4 Hz), 7.57
(1H, s), 7.15-7.02 (2H, m), 6.90-6.80 (1H, m), 2.15 (3H, s),
1.82-1.68 (1H, m), 0.78-0.47 (4H, m). Appearance: amorphous.
EXAMPLE 555
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-chloro-3-nitrobenzoate (Compound No. 3200)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.69 (1H, d, J=1.8
Hz), 8.33 (1H, dd, J=8.4, 1.8 Hz), 7.78 (1H, d, J=8.4 Hz), 7.57
(1H, s), 7.10-7.05 (2H, m), 6.87-6.82 (1H, m), 2.14 (3H, s),
1.77-1.69 (1H, m), 0.75-0.56 (4H, m). Appearance: amorphous.
EXAMPLE 556
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,5-difluorobenzoate (Compound No. 3217)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.80-7.65 (2H, m),
7.58 (1H, s), 7.32-7.00 (3H, m), 6.90-6.80 (1H, m), 2.15 (3H, s),
1.85-1.65 (1H, m), 0.80-0.50 (4H, m). Appearance: amorphous.
EXAMPLE 557
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,5-dichlorobenzoate (Compound No. 3226)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.07 (2H, d, J=2.0
Hz), 7.69 (1H, t, J=2.0 Hz), 7.55 (1H, s), 7.13-7.00 (2H, m),
6.89-6.82 (1H, m), 2.15 (3H, s), 1.83-1.60 (1H, m), 0.80-0.70 (2H,
m), 0.63-0.55 (2H, m). Melting point (.degree. C.): 168-174.
EXAMPLE 558
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,5-dimethylbenzoate (Compound No. 3243)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.82 (2H, s), 7.56
(1H, s) 7.32 (1H, s,), 7.13-7.04 (2H, m), 6.89-6.82 (1H, m), 2.41
(6H, s), 2.16 (3H, s), 1.85-1.72 (1H, m), 0.80-0.70 (2H, m),
0.63-0.53 (2H, m). Melting point (.degree. C.): 117-119.
EXAMPLE 559
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,5-dimethoxybenzoate (Compound No. 3252)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s), 7.34
(1H, s) 7.33 (1H, s), 7.08-7.06 (2H, m), 6.87-6.82 (1H, m),
6.78-6.75 (1H, m), 3.86 (6H, s), 2.16 (3H, s), 1.86-1.72 (1H, m),
0.80-0.72 (2H, m), 0.63-0.54 (2H, m). Appearance: paste state.
EXAMPLE 560
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,4,6-trichlorobenzoate (Compound No. 3258)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.55 (1H, s), 7.46
(2H, s) 7.15-7.05 (2H, m), 6.90-6.82 (1H, m), 2.16 (3H, s),
1.86-1.72 (1H, m), 0.78-0.67 (2H, m), 0.65-0.55 (2H, m).
Appearance: paste state.
EXAMPLE 561
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3,4,5-trimethoxybenzoate (Compound No. 3264)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s), 7.45
(2H, s), 7.14-7.04 (2H, m), 6.89-6.83 (1H, m), 3.96 (3H, s), 3.94
(6H, s), 2.16 (3H, s), 1.85-1.72 (1H, m), 0.80-0.67 (2H, m),
0.63-0.54 (2H, m). Appearance: amorphous.
EXAMPLE 562
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-naphthoate (Compound No. 3270)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.02 (1H, d, J=8.4
Hz), 8.55 (1H, d, J=7.3 Hz), 8.17 (1H, d, J=8.0 Hz), 7.95 (1H, d,
J=8.0 Hz), 7.75-7.54 (4H, m), 7.13-7.00 (2H, m), 6.90-6.80 (1H, m),
2.18 (3H, s), 1.93-1.75 (1H, m), 0.83-0.52 (4H, m). Appearance:
amorphous.
EXAMPLE 563
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-naphthoate (Compound No. 3276)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.81 (1H, s), 8.18
(1H, dd, J=1.5 Hz, 8.5 Hz), 8.05-7.87 (3H, m), 7.70-7.52 (3H, m),
7.10-7.00 (2H, m), 6.90-6.77 (1H, m), 2.18 (3H, s), 1.90-1.73 (1H,
m), 0.83-0.53 (4H, m). Appearance: amorphous.
EXAMPLE 564
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-methyl-1H-pyrrole-2-carboxylate (Compound No. 3282)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s), 7.25
(1H, s), 7.08-7.06 (2H, m), 6.96 (1H, s), 6.86-6.81 (1H, m),
6.24-6.21 (1H, m), 3.97 (3H, s), 2.15 (3H, s), 1.87-1.72 (1H, m),
0.80-0.70 (2H, m), 0.63-0.52 (2H, m). Melting point (.degree. C.):
143-144.
EXAMPLE 565
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-bromo-2-furoate (Compound No. 3288)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.53 (1H, s), 7.43
(1H, d, J=3.7 Hz), 7.15-7.03 (2H, m), 6.90-6.78 (1H, m), 6.59 (1H,
d, J=3.7 Hz), 2.15 (3H, s), 1.83-1.70 (1H, m), 0.80-0.50 (4H, m).
Appearance: caramel-like.
EXAMPLE 566
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl 3-furoate
(Compound No. 3294)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.30 (1H, t, J=0.7
Hz), 7.57-7.53 (1H, m), 7.55 (1H, s), 7.13-7.04 (2H, m), 6.92-6.81
(2H, m), 2.15 (3H, s), 1.83-1.69 (1H, s), 0.80-0.53 (4H, m).
Appearance: paste state.
EXAMPLE 567
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-tert-butyl-2-methyl-3-furoate (Compound No. 3300)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.09-7.07 (2H, m), 6.87-6.83 (1H, m), 6.33 (1H, s), 2.64 (3H, s),
2.15 (3H, s), 1.78-1.73 (1H, m), 1.29 (9H, s), 0.75-0.57 (4H, m).
Appearance: caramel-like.
EXAMPLE 568
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-methyl-2-(trifluoromethyl)-3-furoate (Compound No. 3306)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.53 (1H, s),
7.13-7.04 (2H, m), 6.89-6.82 (1H, m), 6.64 (1H, s), 2.42 (3H, s),
2.13 (3H, s), 1.81-1.67 (1H, m), 0.78-0.68 (2H, m), 0.65-0.53 (2H,
m). Appearance: paste state.
EXAMPLE 569
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-(4-chlorophenyl)-2-(trifluoromethyl)-3-furoate (Compound No.
3312)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.70-7.66 (2H, m),
7.56 (1H, s), 7.47-7.42 (2H, m), 7.19 (1H, s), 7.14-7.05 (2H, m),
6.90-6.82 (1H, m), 2.14 (3H, s), 1.83-1.69 (1H, m), 0.80-0.68 (2H,
m), 0.65-0.53 (2H, m). Appearance: paste state.
EXAMPLE 570
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-chloro-2-thiophenecarboxylate (Compound No. 3318)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.68 (1H, d, J=5.5
Hz), 7.58 (1H, s), 7.14 (1H, d, J=5.5 Hz), 7.11-7.03 (2H, m),
6.90-6.80 (1H, m), 2.16 (3H, s), 1.85-1.70 (1H, m), 0.85-0.50 (4H,
m). Appearance: caramel-like.
EXAMPLE 571
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-methyl-2-thiophenecarboxylate (Compound No. 3324)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.65-7.55 (2H, m),
7.13-6.95 (3H, m), 6.90-6.80 (1H, m), 2.63 (3H, s), 2.16 (3H, s),
1.90-1.70 (1H, m), 0.85-0.50 (4H, m). Appearance: amorphous.
EXAMPLE 572
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-ethoxy-2-thiophenecarboxylate (Compound No. 3330)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.62 (1H, s), 7.59
(1H, d, J=5.5 Hz), 7.08-7.06 (2H, m), 6.90 (1H, d, J=5.5 Hz),
6.86-6.81 (1H, m), 4.26 (2H, q, J=7.0 Hz), 2.17 (3H, s), 1.86-1.75
(1H, m), 1.46 (3H, t, J=7.0 Hz), 0.75-0.55 (4H, m). Appearance:
caramel-like.
EXAMPLE 573
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-chloro-2-thiophenecarboxylate (Compound No. 3336)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.86 (1H, d, J=4.0
Hz), 7.57 (1H, s), 7.14-7.03 (3H, m), 6.90-6.83 (1H, m), 2.15 (3H,
m), 1.83-1.68 (1H, m), 0.80-0.68 (2H, m), 0.65-0.53 (2H, m).
Appearance: paste state.
EXAMPLE 574
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-bromo-2-thiophenecarboxylate (Compound No. 3342)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.80 (1H, d, J=4.0
Hz), 7.57 (1H, s), 7.19 (1H, d, J=4.0 Hz), 7.10-7.00 (2H, m),
6.90-6.80 (1H, m), 2.15 (3H, s), 1.85-1.65 (1H, m), 0.80-0.50 (4H,
m). Appearance: caramel-like.
EXAMPLE 575
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-methyl-2-thiophenecarboxylate (Compound No. 3348)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.87 (1H, d, J=3.7
Hz), 7.57 (1H, s), 7.12-7.00 (2H, m), 6.93-6.87 (2H, m), 2.58 (3H,
s), 2.15 (3H, s), 1.85-1.70 (1H, m), 0.80-0.50 (4H, m). Appearance:
caramel-like.
EXAMPLE 576
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-acetyl-2-thiophenecarboxylate (Compound No. 3354)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.02 (1H, d, J=4.0
Hz), 7.72 (1H, d, J=4.0 Hz), 7.58 (1H, s), 7.10-7.07 (2H, m),
6.87-6.83 (1H, m), 2.63 (3H, s), 2.15 (3H, s), 1.79-1.71 (1H, m),
0.75-0.56 (4H, m). Appearance: amorphous.
EXAMPLE 577
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-nitro-3-thiophenecarboxylate (Compound No. 3360)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.52 (1H, d, J=1.8
Hz), 8.43 (1H, d, J=1.8 Hz), 7.56 (1H, s), 7.13-7.05 (2H, m),
6.90-6.80 (1H, m), 2.14 (3H, s), 1.85-1.65 (1H, m), 0.85-0.50 (4H,
m). Appearance: amorphous.
EXAMPLE 578
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4,5-dibromo-2-thiophenecarboxylate (Compound No. 3366)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.84 (1H, s), 7.56
(1H, s) 7.14-7.05 (2H, m), 6.90-6.83 (1H, m), 2.14 (3H, s),
1.83-1.69 (1H, m), 0.79-0.68 (2H, m), 0.65-0.55 (2H, m).
Appearance: amorphous.
EXAMPLE 579
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-thiophenecarboxylate (Compound No. 3372)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.42-8.40 (1H, m),
7.70-7.66 (1H, m), 7.58 (1H, s), 7.47-7.41 (1H, m), 7.13-7.05 (2H,
m), 6.88-6.82 (1H, m), 2.15 (3H, s), 1.84-1.70 (1H, m), 0.80-0.68
(2H, m), 0.64-0.55 (2H, m). Appearance: paste state.
EXAMPLE 580
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methoxy-3-thiophenecarboxylate (Compound No. 3378)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.33 (1H, d, J=3.5
Hz), 7.59 (1H, s), 7.09-7.06 (2H, m), 6.87-6.82 (1H, m), 6.38 (1H,
d, J=3.5 Hz), 3.93 (3H, s), 2.16 (3H, s), 1.82-1.74 (1H, m),
0.75-0.56 (4H, m). Melting point (.degree. C.): 146-149.
EXAMPLE 581
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-benzyl-3-tert-butyl-1H-pyrazole-5-carboxylate (Compound No.
3384)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.44 (1H, s), 7.21
(5H, s), 7.09-7.06 (2H, m), 6.98 (1H, s), 6.85-6.80 (1H, m), 5.72
(2H, s), 2.08 (3H, s), 1.76-1.64 (1H, m), 1.36 (9H, s), 0.75-0.64
(2H, m), 0.59-0.50 (2H, m). Appearance: paste state.
EXAMPLE 582
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-chloro-1,3-dimethyl-1H-pyrazole-4-carboxylate (Compound No.
3390)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.62 (1H, s),
7.09-7.07 (2H, m), 6.87-6.82 (1H, m), 3.86 (3H, s), 2.52 (3H, s),
2.14 (3H, s), 1.84-1.77 (1H, m), 0.75-0.67 (2H, m), 0.60-0.53 (2H,
m). Appearance: paste state.
EXAMPLE 583
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-(2-chlorophenyl)-5-methyl-4-isoxazolecarboxylate (Compound No.
3396)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.53 (1H, s),
7.48-7.42 (2H, m), 7.41-7.30 (2H, m), 7.08-7.06 (2H, m), 6.83-6.78
(1H, m), 2.89 (3H, s), 2.02 (3H, s), 1.67-1.53 (1H, m), 0.68-0.50
(4H, m). Appearance: amorphous.
EXAMPLE 584
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-methyl-1,2,3-thiadizaole-5-carboxylate (Compound No. 3402)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.15-7.05 (2H, m), 6.91-6.84 (1H, m), 3.08 (3H, s), 2.14 (3H, s),
1.80-1.65 (1H, m), 0.80-0.72 (2H, m), 0.64-0.53 (2H, m).
Appearance: paste state.
EXAMPLE 585
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
6-methyl-2-pyridinecarboxylate (Compound No. 3408)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.12 (1H, d, J=7.7
Hz), 7.82 (1H, t, J=7.7 Hz), 7.55 (1H, s), 7.46 (1H, d, J=7.7 Hz),
7.12-7.02 (2H, m), 6.85-6.76 (1H, m), 2.71 (3H, s), 2.15 (3H, s),
1.87-1.74 (1H, m), 0.82-0.52 (4H, m). Appearance: caramel-like.
EXAMPLE 586
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5-butyl-2-pyridinecarboxylate (Compound No. 3414)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.67 (1H, br.s),
8.22 (1H, d, J=7.7 Hz), 7.74 (1H, br.d, J=7.7 Hz), 7.53 (1H, s),
7.08-7.05 (2H, m), 6.83-6.78 (1H, m), 2.75 (2H, t, J=7.7 Hz), 2.15
(3H, s), 1.84-1.59 (3H, m), 1.48-1.32 (2H, m), 0.95 (3H, t, J=7.0
Hz), 0.75-0.54 (4H, m). Appearance: caramel-like.
EXAMPLE 587
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl nicotinate
(Compound No. 3420)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.42-9.41 (1H, m),
8.91 (1H, dd, J=4.8, 0.8 Hz), 8.50-8.44 (1H, m), 7.60 (1H, s),
7.56-7.49 (1H, m), 7.13-7.04 (2H, m), 6.88-6.78 (1H, m), 2.15 (3H,
s), 1.90-1.70 (1H, m), 0.81-0.70 (2H, m), 0.63-0.55 (2H, m).
Appearance: paste state.
EXAMPLE 588
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-chloronicotinate (Compound No. 3426)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.66 (1H, dd, J=4.8,
2.0 Hz), 8.45 (1H, dd, J=7.7, 2.0 Hz), 7.59 (1H, s), 7.45 (1H, dd,
J=7.7, 4.8 Hz), 7.14-7.06 (2H, m), 6.89-6.83 (1H, m), 2.15 (3H, s),
1.84-1.70 (1H, m), 0.80-0.52 (4H, m). Appearance: caramel-like.
EXAMPLE 589
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-methylnicotinate (Compound No. 3432)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.74 (1H, dd, J=4.8,
1.5 Hz), 8,46 (1H, dd, J=7.7, 1.5 Hz), 7.58 (1H, s), 7.34 (1H, dd,
J=7.7, 4.8 Hz), 7.13-7.05 (2H, m), 6.89-6.83 (1H, m), 2.93 (3H, s),
2.15 (3H, s), 1.83-1.67 (1H, m), 0.80-0.68 (2H, m), 0.65-0.55 (2H,
m). Appearance: paste state.
EXAMPLE 590
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-phenoxynicotinate (Compound No. 3438)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.50 (1H, dd, J=7.8,
2.2 Hz), 8.39 (1H, dd, J=4.8, 2.2 Hz), 7.61 (1H, s), 7.46-7.38 (2H,
m), 7.29-7.20 (1H, m), 7.19-7.04 (5H, m), 6.86-6.81 (1H, m), 2.14
(3H, s), 1.85-1.72 (1H, m), 1.36 (9H, s), 0.75-0.65 (2H, m),
0.58-0.52 (2H, m). Appearance: paste state.
EXAMPLE 591
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-(methylsulfanyl)nicotinate (Compound No. 3444)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.70 (1H, dd, J=4.9,
1.8 Hz), 8.47 (1H, dd, J=7.7, 1.8 Hz), 7.63 (1H, s), 7.16 (1H, dd,
J=7.7, 4.8 Hz) 7.12-7.05 (2H, m), 6.89-6.82 (1H, m), 2.59 (3H, s),
2.16 (3H, s), 1.84-1.71 (1H, m), 0.80-0.70 (2H, m), 0.65-0.53 (2H,
m). Appearance: paste state.
EXAMPLE 592
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-(allylsulfanyl)nicotinate (Compound No. 3450)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.67 (1H, dd, J=4.8,
1.8 Hz), 8.46 (1H, dd, J=8.2, 1.8 Hz), 7.62 (1H, s), 7.16 (1H, dd,
J=8.2, 4.8 Hz), 7.09-7.04 (2H, m), 6.89-6.82 (1H, m), 6.10-5.90
(1H, m), 5.33 (1H, dd, J=16.8, 1.6 Hz), 5.12 (1H, dd, J=11.0, 1.2
Hz), 3.91 (1H, dd, J=6.8, 1.2 Hz), 2.15 (3H, s), 1.85-1.70 (1H, m),
0.78-0.71 (2H, m), 0.60-0.51 (2H, m). Appearance: paste state.
EXAMPLE 593
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-(phenylsulfanyl)nicotinate (Compound No. 3456)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.50 (1H, s), 8.47
(1H, d, J=2.6 Hz), 7.65 (1H, s), 7.59-7.51 (2H, m), 7.48-7.41 (3H,
m), 7.17-7.05 (3H, m), 6.90-6.82 (1H, m), 2.18 (3H, s), 1.89-1.74
(1H, m), 0.82-0.70 (2H, m), 0.65-0.54 (2H, m). Appearance: paste
state.
EXAMPLE 594
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(trifluoromethyl)nicotinate (Compound No. 3462)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.42 (1H, s), 9.08
(1H, d, J=5.1 Hz), 7.79 (1H, d, J=5.1 Hz), 7.57 (1H, s), 7.14-7.06
(2H, m), 6.90-6.84 (1H, m), 2.16 (3H, s), 1.84-1.72 (1H, m),
0.79-0.71 (2H, m), 0.63-0.55 (2H, m). Melting point (.degree. C.):
92-93.
EXAMPLE 595
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
6-chloronicotinate (Compound No. 3468)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.19 (1H, d, J=2.0),
8.40 (1H, dd, J=8.4, 2.6), 7.59 (1H, s), 7.54 (1H, d, J=8.4 Hz),
7.10-7.08 (1H, m), 7.07 (1H, s), 6.87-6.82 (1H, m), 2.14 (3H, s),
1.79-1.65 (1H, m), 0.79-0.70 (2H, m), 0.62-0.53 (2H, m).
Appearance: paste state.
EXAMPLE 596
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,6-dichloronicotinate (Compound No. 3474)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.46 (1H, d, J=8.1
Hz), 7.67 (1H, s), 7.52 (1H, d, J=8.1 Hz), 7.13-7.02 (2H, m),
6.90-6.75 (1H, m), 2.14 (3H, s), 1.85-1.68 (1H, m), 0.85-0.48 (4H,
m). Appearance: amorphous.
EXAMPLE 597
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-chloro-6-methylnicotinate (Compound No. 3480)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.37 (1H, d, J=7.7
Hz), 7.58 (1H, s), 7.27 (1H, d, J=7.7 Hz), 7.14-7.08 (2H, m),
6.89-6.80 (1H, m), 2.65 (3H, s), 2.15 (3H, s), 1.83-1.69 (1H, m),
0.80-0.70 (2H, m), 0.68-0.55 (2H, m). Appearance: paste state.
EXAMPLE 598
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
5,6-dichloronicotinate (Compound No. 3486)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.07 (1H, d, J=2.2
Hz), 8.50 (1H, d, J=2.2 Hz), 7.57 (1H, s), 7.10-7.07 (2H, m),
6.87-6.82 (1H, m), 2.13 (3H, s), 1.80-1.65 (1H, m), 0.75-0.70 (2H,
m), 0.58-0.55 (2H, m). Appearance: paste state.
EXAMPLE 599
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2-chloroisonicotinate (Compound No. 3492)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.68 (1H, d, J=5.0
Hz), 8.05 (1H, s), 7.95-7.92 (1H, m), 7.57 (1H, s), 7.10-7.07 (2H,
m), 6.87-6.83 (1H, m), 2.14 (3H, s), 1.77-1.68 (1H, m), 0.75-0.71
(2H, m), 0.58-0.56 (2H, m). Appearance: paste state.
EXAMPLE 600
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-benzofuran-2-carboxylate (Compound No. 3498).
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.86-7.75 (2H, m),
7.68-7.51 (3H, m), 7.38 (1H, dd, J=7.7, 7.0 Hz), 7.12-7.05 (2H, m),
6.89-6.80 (1H, m), 2.17 (3H, s), 1.86-1.73 (1H, m), 0.80-0.68 (2H,
m), 0.64-0.55 (2H, m). Appearance: amorphous.
EXAMPLE 601
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-benzothiophene-2-carboxylate (Compound No. 3504)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.34 (1H, s), 7.94
(2H, m), 7.64 (1H, s), 7.59-7.42 (2H, m), 7.09-7.07 (2H, m),
6.87-6.83 (1H, m), 2.18 (3H, s), 1.88-1.72 (1H, m), 0.77-0.71 (2H,
m), 0.61-0.53 (2H, m). Melting point (.degree. C.): 105-107.
EXAMPLE 602
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1,3-benzothiazole-6-carboxylate (Compound No. 3510)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 9.24 (1H, s), 8.89
(1H, d, J=1.4 Hz), 8.36 (1H, dd, J=8.4, 1.4 Hz), 8.28 (1H, d, J=8.4
Hz), 7.65 (1H, s), 7.09-7.06 (2H, m), 6.87-6.82 (1H, m), 2.17 (3H,
s), 1.86-1.73 (1H, m), 0.78-0.72 (2H, m), 0.63-0.55 (2H, m).
Appearance: amorphous.
EXAMPLE 603
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1,3-benzodioxole-5-carboxylate (Compound No. 3516)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.85 (1H, dd, J=8.4,
1.8 Hz), 7.60-7.59 (2H, m), 7.09-7.06 (2H, m), 6.93 (1H, d, J=8.0
Hz), 6.86-6.82 (1H, m), 6.10 (2H, s), 2.15 (3H, s), 1.86-1.74 (1H,
m), 0.79-0.70 (2H, m), 0.62-0.53 (2H, m). Appearance: paste
state.
EXAMPLE 604
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-isoquinolinecarboxylate (Compound No. 3522)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.45 (1H, d, J=8.1
Hz), 7.78-7.70 (2H, m), 7.61-7.53 (2H, m), 7.16 (1H, d, J=7.7 Hz),
7.12-7.05 (2H, m), 6.90-6.83 (1H, m), 6.66 (1H, d, J=7.3 Hz), 2.15
(3H, s), 1.81-1.66 (1H, m), 0.79-0.67 (2H, m), 0.63-0.53 (2H, m).
Appearance: amorphous.
EXAMPLE 605
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
tert-butyl(methyl)carbamate (Compound No. 3528)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.51 (1H, s),
7.15-7.03 (2H, m), 6.90-6.80 (1H, m), 3.11 (3H, s), 2.14 (3H, s),
1.85-1.70 (1H, m), 1.47 (9H, S), 0.80-0.50 (4H, m) Melting point
(.degree. C.): 113-115.
EXAMPLE 606
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
dibutylcarbamate (Compound No. 3534)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.15-7.03 (2H, m), 6.90-6.78 (1H, m), 3.50-3.26 (4H, m), 2.13 (3H,
s), 1.87-1.50 (5H, m), 1.50-1.15 (4H, m), 1.10-0.85 (6H, m),
0.80-0.54 (4H, m). Appearance: caramel-like.
EXAMPLE 607
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
benzyl(methyl)carbamate (Compound No. 3540)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (0.5H, s), 7.57
(0.5H, s), 7.40-7.20 (5H, m), 7.15-7.03 (2H, m), 6.92-6.80 (1H, m),
4.68 (1H, s), 4.57 (1H, s), 3.08 (1.5H, s), 3.02 (1.5H, s), 2.15
(1.5H, s), 2.13 (1.5H, s), 1.85-1.65 (1H, m), 0.80-0.45 (4H, m).
Appearance: caramel-like.
EXAMPLE 608
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
cyanomethyl(methyl)carbamate (Compound No. 3546)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (0.4H, s), 7.56
(0.6H, s), 7.15-7.04 (2H, m), 6.90-6.80 (1H, m), 4.42 (0.8H, s),
4.36 (1.2H, s), 3.30 (1.8H, s), 3.19 (1.2H, s), 2.14 (3H, s),
1.85-1.62 (1H, m), 0.80-0.53 (4H, m). Appearance: caramel-like.
EXAMPLE 609
Ethyl
N-({[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]oxy}ca-
rbonyl)-N-methylglycinate (Compound No. 3552)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.61 (0.5H, s), 7.60
(0.5H, s), 7.15-7.02 (2H, m), 6.90-6.80 (1H, m), 4.28-4.11 (4H, m),
3.23 (1.5H, s), 3.13 (1.5H, s), 2.15 (1.5H, s), 2.13 (1.5H, s),
1.85-1.65 (1H, m), 1.31-1.18 (3H, m), 0.80-0.50 (4H, m) Appearance:
caramel-like.
EXAMPLE 610
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
methyl(2-pyridinyl)carbamate (Compound No. 3558)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.35-8.25 (1H, m),
7.70-7.55 (1H, m), 7.05-6.90 (5H, m), 6.85-6.74 (1H, m), 3.56 (3H,
s), 2.03 (3H, s), 1.72-1.55 (1H, m), 0.75-0.45 (4H, m). Melting
point (.degree. C.): 140-147.
EXAMPLE 611
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-piperidinecarboxylate (Compound No. 3636)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56 (1H, s),
7.15-7.03 (2H, m), 6.90-6.80 (1H, m), 3.70-3.60 (2H, m), 3.60-3.45
(2H, m), 2.15 (3H, s), 1.86-1.70 (1H, m), 1.70-1.50 (6H, m),
0.80-0.53 (4H, m). Appearance: caramel-like.
EXAMPLE 612
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
bis(2-chloroethyl)carbamate (Compound No. 3570)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.58 (1H, s),
7.15-7.05 (2H, m), 6.92-6.82 (1H, m), 3.98-3.70 (8H, m), 2.13 (3H,
s), 1.82-1.65 (1H, m), 0.80-0.50 (4H, m). Melting point (.degree.
C.): 166-167.
EXAMPLE 613
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
diallylcarbamate (Compound No. 3576)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.56 (1H, s),
7.12-7.04 (2H, m), 6.88-6.80 (1H, m), 6.00-5.70 (2H, m), 5.30-5.15
(4H, m), 4.10-3.93 (4H, m), 2.13 (3H, s), 1.85-1.68 (1H, m),
0.80-0.52 (4H, m). Appearance: caramel-like.
EXAMPLE 614
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
bis(cyanomethyl)carbamate (Compound No. 3582)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (1H, s),
7.18-7.05 (2H, m), 6.90-6.80 (1H, m), 4.54 (2H, s), 4.48 (2H, s),
2.13 (3H, s), 1.80-1.65 (1H, m), 0.80-0.50 (4H, m). Appearance:
caramel-like.
EXAMPLE 615
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
bis(2-cyanoethyl)carbamate (Compound No. 3588)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.61 (1H, s),
7.18-7.05 (2H, m), 6.92-6.82 (1H, m), 3.91 (2H, t, J=6.6 Hz), 3.77
(2H, t, J=6.2 Hz), 2.85 (2H, t, J=6.6 Hz), 2.78 (2H, t, J=6.2 Hz),
2.13 (3H, s), 1.80-1.63 (1H, m), 0.82-0.53 (4H, m). Melting point
(.degree. C.): 159-161.
EXAMPLE 616
Ethyl
N-({[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]oxy}ca-
rbonyl)-N-(2-ethoxy-2-oxoethyl)glycinate (Compound No. 3594)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.65 (1H, s),
7.13-7.03 (2H, m), 6.90-6.80 (1H, m), 4.33-4.05 (8H, m), 2.12 (3H,
s), 1.83-1.65 (1H, m), 1.28 (3H, t, J=7.3 Hz), 1.19 (3H, t, J=7.3
Hz), 0.80-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 617
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
bis(2-methoxyethyl)carbamate (Compound No. 3600)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (1H, s),
7.15-7.05 (2H, m), 6.90-6.80 (1H, m), 3.80-3.50 (8H, m), 3.32 (6H,
s), 2.15 (3H, s), 1.86-1.69 (1H, m), 0.80-0.52 (4H, m). Appearance:
caramel-like.
EXAMPLE 618
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
bis(2-ethoxyethyl)carbamate (Compound No. 3606)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.57 (1H, s),
7.15-7.03 (2H, m), 6.90-6.80 (1H, m), 3.78-3.55 (8H, m), 3.46 (4H,
q, J=6.9 Hz), 2.14 (3H, s), 1.87-1.65 (1H, m), 1.15 (3H, t, J=6.9
Hz), 1.14 (3H, t, J=6.9 Hz), 0.80-0.53 (4H, m). Appearance:
caramel-like.
EXAMPLE 619
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-azetizinecarboxylate (Compound No. 3612)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.53 (1H, s),
7.13-7.02 (2H, m), 6.90-6.78 (1H, m), 4.38-4.05 (4H, m), 2.45-2.29
(2H, m), 2.15 (3H, s), 1.85-1.67 (1H, m), 0.80-0.50 (4H, m).
Melting point (.degree. C.): 134-136.
EXAMPLE 620
1-[6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
2-methyl 1,2-pyrrolidinedicarboxylate (Compound No. 3618)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.65 (0.5H, s), 7.62
(0.5H, s), 7.15-7.02 (2H, m), 6.90-6.78 (1H, m), 4.63-4.57 (0.5H,
m), 4.51-4.44 (0.5H, m), 3.91-3.55 (2H, m), 3.75 (1.5H, s), 3.65
(1.5H, s), 2.50-1.90 (4H, m), 2.15 (1.5H, s), 2.13 (1.5H, s),
1.90-1.69 (1H, m), 0.80-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 621
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
3-hydroxy-1-pyrrolidinecarboxylate (Compound No. 3624)
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.60 (1H, s),
7.13-7.03 (2H, m), 6.90-6.80 (1H, m), 4.65-4.52 (1H, m), 3.85-3.55
(4H, m), 2.14 (3H, s), 2.13-2.00 (2H, m), 1.87-1.70 (2H, m),
0.80-0.50 (4H, m). Appearance: caramel-like.
EXAMPLE 622
6-Chloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 1126)
(1) 2,3,5-Trimethylphenyl acetate
In dichloromethane (150 mL) was dissolved 15.09 g (0.1108 mol) of
2,3,5-trimethylphenol, and 17.82 mL (0.2204 mol) of pyridine, then
20.78 mL (0.2202 mol) of acetic anhydride were added to the
solution, and the mixture was stirred at room temperature
overnight. The reaction mixture was poured into water, and
extracted with dichloro-methane. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was removed, and the residue was purified by
silica gel column chromatography (Wako gel C-100, hexane:ethyl
acetate, gradient) to obtain 20.08 g (0.1127 mol, Yield:
quantitative) of 2,3,5-trimethylphenyl acetate.
(2) 1-(2-Hydroxy-3,4,6-trimethylphenyl)ethanone
To 13.83 g (77.60 mmol) of 2,3,5-trimethylphenyl acetate obtained
in (1) was added 20.69 g (155.2 mmol) of aluminum chloride little
by little in an ice bath with stirring. The mixture was stirred
while heating to 100.degree. C. overnight. After cooling, the
reaction mixture was added to ice water little by little. The
mixture was extracted with dichloromethane, the organic layers were
combined, washed with water, and dried over anhydrous magnesium
sulfate. The solvent was removed, and the residue was purified by
silica gel column chromatography (Wako gel C-100, hexane:ethyl
acetate, gradient) to obtain 12.75 g (71.55 mmol, Yield: 92.20%) of
1-(2-hydroxy-3,4,6-trimethylphenyl)ethanone.
(3) 1-(2-Methoxy-3,4,6-trimethylphenyl)ethanone
In acetone (100 mL) was dissolved 8.00 g (44.9 mmol) of
1-(2-hydroxy-3,4,6-trimethylphenyl)ethanone obtained in (2), to the
mixture were added 18.6 g (135 mmol) of potassium carbonate, and
then, 8.40 mL (135 mmol) of methyl iodide, and the resulting
mixture was refluxed for 27 hours and 30 minutes. Moreover, 18.6 g
(135 mmol) of potassium carbonate, and 8.40 mL (135 mmol) of methyl
iodide were additionally added to the mixture, and the resulting
mixture was refluxed for 6 hours. The reaction mixture was
concentrated under reduced pressure, water (100 mL) was added to
the residue, and the mixture was extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (Daisogel 1001W, hexane:ethyl acetate, gradient) to
obtain 8.04 g (41.9 mmol, Yield: 93.3%) of
1-(2-methoxy-3,4,6-trimethylphenyl)ethanone.
(4) 1-(2-Methoxy-3,4,6-trimethylphenyl)ethanol
In methanol (100 mL) was dissolved 5.01 g (26.1 mmol) of
1-(2-methoxy-3,4,6-trimethylphenyl)ethanone obtained in (3), and in
an ice bath, 1.00 g (26.5 mmol) of sodium borohydride was added to
the solution and the mixture was stirred in an ice bath for 2 hours
and 30 minutes. The reaction mixture was poured into 400 mL of ice
water, and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous sodium sulfate. The solvent was removed to obtain 4.35g
(22.4 mmol, Yield: 85.8%) of
1-(2-methoxy-3,4,6-trimethylphenyl)ethanol.
(5) 2-(1-Chloroethyl)-3-methoxy-1,4,5-trimethylbenzene
To 0.652 g (3.36 mmol) of
1-(2-methoxy-3,4,6-trimethylphenyl)ethanol obtained in (4) was
added dropwise with stirring 0.150 mL (1.72 mmol) of oxalyl
chloride, and the mixture was stirred at 100.degree. C. for 2
hours. Then, dichloromethane (1 mL) and triethylamine (3 mL) were
added to the reaction mixture, and the resulting mixture was
stirred at 100.degree. C. for 3 hours. The reaction mixture was
poured into 60 ml of ice water, and extracted with ethyl acetate.
The organic layers were combined, washed successively with water
and brine, and dried over anhydrous sodium sulfate. The solvent was
removed to obtain 0.620 g (2.91 mmol, Yield: 86.6%) of
2-(1-chloroethyl)-3-methoxy-1,4,5-trimethylbenzene.
(6) 3-Methoxy-1,2,5-trimethyl-4-vinylbenzene
In N,N-dimethylformamide (DMF, 6 mL) was dissolved 0.620 g (2.91
mmol) of 2-(1-chloroethyl)-3-methoxy-1,4,5-trimethylbenzene
obtained in (5), and 1.20 g (8.70 mmol) of potassium carbonate was
added to the solution and the resulting mixture was refluxed for 9
hours. The reaction mixture was poured into 50 ml of ice water, and
extracted with hexane. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the residue was purified by
silica gel column chromatography (Daisogel 1001W, hexane:ethyl
acetate, gradient) to obtain 0.360 g (2.05 mmol, Yield: 70.4%) of
3-methoxy-1,2,5-trimethyl-4-vinylbenzene.
(7) 2-Cyclopropyl-3-methoxy-1,4,5-trimethylbenzene
To dry dichloromethane (5 mL) was added 3.07 mL (3.04 mmol) of
diethyl zinc (0.99 mol/L hexane solution), a dichloromethane (2.5
mL) solution containing 0.23 mL (3.0 mmol) of trifluoroacetic acid
was gradually added dropwise with stirring in an ice bath. After
completion of the dropwise addition, the mixture was stirred in an
ice bath for 30 minutes, and 0.24 mL (3.0 mmol) of diiodomethane
was added dropwise to the mixture. Then, a dichloromethane (3 mL)
solution containing 0.268 g (1.52 mmol) of
3-methoxy-1,2,5-trimethyl-4-vinylbenzene obtained in (6) was added
dropwise, and the mixture was stirred in an ice bath for 1 hour.
The reaction mixture was poured into water, made acidic with
diluted hydrochloric acid, and then, extracted with
dichloromethane. The organic layers were combined, washed with
water, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05717, 2
plates were used, developed by hexane:ethyl acetate=25:1) to obtain
0.212 g (1.12 mmol, Yield: 73.7%) of
2-cyclopropyl-3-methoxy-1,4,5-trimethylbenzene.
(8) 2-Cyclopropyl-3,5,6-trimethylphenol
Under nitrogen atmosphere, in dry N,N-dimethylformamide (5 mL) was
suspended 134 mg (3.35 mmol) of 60% sodium hydride, and 0.26 mL
(3.5 mmol) of ethanethiol was gradually added dropwise to the
suspension. After stirring for 30 minutes, a dry
N,N-dimethylformamide (5 mL) solution containing 0.212 g (1.12
mmol) of 2-cyclopropyl-3-methoxy-1,4,5-trimethylbenzene obtained in
(7) was added dropwise to the mixture, and the resulting mixture
was stirred at 160.degree. C. for 5 hours. After allowing to stand
for cooling, the reaction mixture was poured into water, made
acidic by adding diluted hydrochloric acid, and extracted with
ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 3 plates were used, developed
by ethyl acetate:hexane=25:1) to obtain 179 mg (1.02 mmol, Yield:
91.1%) of 2-cyclopropyl-3,5,6-trimethylphenol.
(9) Mixture of
6-chloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine 1-oxide
and 3-chloro-6-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine
1-oxide (Step B-2)
179 mg (1.02 mmol) of 2-cyclopropyl-3,5,6-trimethylphenol,
1,4-dioxane (5 mL) and dimethylsulfoxide (5 mL) were mixed, 125 mg
(1.12 mmol) of potassium tert-butoxide was added to the mixture,
and the resulting mixture was stirred for 10 minutes. To the
mixture was added 167 mg (1.01 mmol) of 3,6-dichloropyridazine
1-oxide, and the mixture was allowed to stand at room temperature
for 3 days. The reaction mixture was poured into water, and
extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05717, 2 plates were used, developed
by hexane:ethyl acetate=2:1) to obtain 263 mg of a mixture of
6-chloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine 1-oxide
and 3-chloro-6-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine
1-oxide.
(10)
4,6-Dichloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine
(Step B-3)
263 mg of a mixture of
6-chloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine 1-oxide
and 3-chloro-6-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine
1-oxide obtained in (9) and 3.0 mL (32 mmol) of phosphorus
oxychloride were mixed, and the mixture was stirred at room
temperature overnight. Dichloromethane and water were added to the
reaction mixture, and after stirring, the mixture was extracted
with dichloromethane. The organic layers were combined, washed with
water, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05717, 2
plates were used, developed by hexane:ethyl acetate=2:1) to obtain
198 mg (0.613 mmol, Yield from 3,6-dichloropyridazine 1-oxide:
60.7%) of
4,6-dichloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine.
Also, 43.8 mg (0.144 mmol, Yield from 3,6-dichloropyridazine
1-oxide: 14.2%) of
3-chloro-6-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine 1-oxide
was obtained.
(11)
6-Chloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 1126, Step A-3 and A-4)
In dimethylsulfoxide (10 mL) was dissolved 198 mg (0.613 mmol) of
4,6-dichloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)pyridazine
obtained in (10), 251 mg (3.06 mmol) of sodium acetate was added to
the solution and the mixture was stirred at 120.degree. C. for 4
hours. The reaction mixture was cooled, poured into water, and made
acidic with diluted hydrochloric acid. The mixture was extracted
with ethyl acetate, the organic layers were combined, washed with
water, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05717, 2
plates were used, developed by hexane:ethyl acetate=1:2) to obtain
116 mg (0.380 mmol, Yield: 62.0%) of
6-chloro-3-(2-cyclopropyl-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 1126).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.67 (1H, s), 6.62
(1H, s), 2.22 (3H, s), 2.16 (3H, s), 2.05 (3H, s), 1.85-1.65 (1H,
m), 0.75-0.62 (2H, m), 0.60-0.45 (2H, m). Melting point (.degree.
C.): 212-219.
EXAMPLE 623
6-Chloro-3-(2-methoxy-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 1128)
(1) 1-[2-(Benzyloxy)-3,4,6-trimethylphenyl]ethanone
In N,N-dimethylformamide (8 mL) was dissolved 2.00 g (11.2 mmol) of
1-(2-hydroxy-3,4,6-trimethylphenyl)ethanone obtained in Example 622
(2). To the solution was added in an ice bath 0.488 g (11.2 mmol)
of 60% sodium hydride, and after stirring in an ice bath for 10
minutes, 1.92 g (11.2 mmol) of benzyl bromide was gradually added
dropwise and the mixture was stirred at room temperature overnight.
The reaction mixture was poured into ice water, and extracted with
ethyl acetate. The organic layer was successively washed with water
and brine, and dried over anhydrous magnesium sulfate. The solvent
was removed, and the obtained residue was purified by silica gel
column chromatography (Wako gel C-100, hexane-ethyl acetate,
gradient) to obtain 2.36 g (8.81 mmol, Yield: 78.7%) of
1-[2-(benzyloxy)-3,4,6-trimethylphenyl]ethanone.
(2) 2-(Benzyloxy)-3,4,6-trimethylphenyl acetate
In dichloromethane (3 mL) was dissolved 500 mg (1.87 mmol) of
1-[2-(benzyloxy)-3,4,6-trimethylphenyl]ethanone obtained in (1), a
dichloromethane (6 mL) solution containing 921 mg (purity 70-75%,
3.73-3.99 mmol) of m-chloroper-benzoic acid was added to the
solution, and the resulting mixture was stirred at room temperature
for 2 days. The reaction mixture was poured into a saturated
aqueous sodium sulfite solution, and extracted with ethyl acetate.
The organic layer was washed with a saturated aqueous sodium
hydrogen carbonate solution, and dried over anhydrous sodium
sulfate. The solvent was removed to obtain 560 mg of
2-(benzyloxy)-3,4,6-trimethylphenyl acetate.
(3) 2-(Benzyloxy)-3,4,6-trimethylphenol
In ethanol (15 mL) was dissolved 560 mg of
2-(benzyloxy)-3,4,6-trimethylphenyl acetate obtained in (2), 2N
aqueous sodium hydroxide solution was added to the solution and the
resulting mixture was stirred at room temperature overnight and at
60.degree. C. for 4 hours. The reaction mixture was cooled up to
room temperature, and poured into water. To the mixture was added
1N hydrochloric acid to make the mixture acidic, and the mixture
was extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane-ethyl acetate, gradient) to obtain 290 mg (1.20 mmol,
Yield from 1-[2-(benzyloxy)-3,4,6-trimethylphenyl]ethanone: 64.2%)
of 2-(benzyloxy)-3,4,6-trimethylphenol.
(4) 3-(Benzyloxy)-2-methoxy-1,4,5-trimethylbenzene
In acetone (3 mL) was dissolved 290 mg (1.20 mmol) of
2-(benzyloxy)-3,4,6-trimethylphenol obtained in (3), 350 mg (2.54
mmol) of potassium carbonate was added to the solution, and the
mixture was stirred at room temperature for 15 minutes. Then, 0.180
mL (2.89 mmol) of methyl iodide was added to the mixture, and the
resulting mixture was stirred at room temperature overnight. The
reaction mixture was poured into water, and extracted with ethyl
acetate. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 3 plates were used, developed by ethyl
acetate:hexane=10:1) to obtain 196 mg (0.766 mmol, Yield: 63.8%) of
3-(benzyloxy)-2-methoxy-1,4,5-trimethylbenzene.
(5) 2-Methoxy-3,5,6-trimethylphenol
In methanol (3 mL) was dissolved 180 mg (0.703 mmol) of
3-(benzyloxy)-2-methoxy-1,4,5-trimethylbenzene obtained in (4),
0.10 g of 5% palladium-carbon was added to the solution, and the
mixture was stirred under hydrogen atmosphere (1 atm) for 4 hours.
The reaction mixture was filtered through Celite, and the filtrate
was concentrated. 90.7 mg (0.546 mmol, Yield: 77.7%) of
2-methoxy-3,5,6-trimethylphenol was obtained.
(6) Mixture of
6-chloro-3-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine 1-oxide
(Step B-2)
90.0 mg (0.542 mmol) of 2-methoxy-3,5,6-trimethylphenol obtained in
(5), 1,4-dioxane (1.5 mL) and dimethylsulfoxide (1.5 mL) were
mixed, 73.5 mg (0.656 mmol) of potassium tert-butoxide was added to
the mixture, and the resulting mixture was stirred in an ice bath
for 15 minutes. To the mixture was added 93.2 mg (0.565 mmol) of
3,6-dichloropyridazine 1-oxide, and the resulting mixture was
stirred at room temperature for 3 hours. The reaction mixture was
poured into water, and extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was distilled
off and the obtained residue was purified by preparative thin-layer
chromatography (available from MERCK CO., 1.05744, 3 plates were
used, developed by hexane:ethyl acetate=2:1) to obtain 140 mg of a
mixture of 6-chloro-3-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine
1-oxide and 3-chloro-6-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine
1-oxide.
(7) 4,6-Dichloro-3-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine
(Step B-3)
140 mg of a mixture of
6-chloro-3-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine 1-oxide
obtained in (6) and 0.25 mL (2.7 mmol) of phosphorus oxychloride
were mixed, and the mixture was stirred at room temperature
overnight. The reaction mixture was poured into water, and
extracted with dichloromethane. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 3 plates were used, developed
by hexane:ethyl acetate=2:1) to obtain 111 mg (0.355 mmol, Yield
from 3,6-dichioropyridazine 1-oxide: 62.8%) of
4,6-dichloro-3-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine. Also,
38.3 mg (0.130 mmol, Yield from 3,6-dichloropyridazine 1-oxide:
23.0%) of 3-chloro-6-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine
1-oxide was obtained.
(8) 6-Chloro-3-(2-methoxy-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 1128, Step B-4)
To a dimethylsulfoxide (10 mL) solution containing 111 mg (0.355
mmol) of
4,6-dichloro-3-(2-methoxy-3,5,6-trimethylphenoxy)pyridazine
obtained in (7) was added 0.3 mL (0.6 mmol) of 2 mol/L aqueous
sodium hydroxide solution, and the mixture was stirred at room
temperature for 2 hours and 30 minutes. The reaction mixture was
poured into ice-cooled 1 mol/L aqueous sodium hydroxide solution,
and extracted with ethyl acetate. The aqueous layer was separated,
made acidic by adding conc. hydrochloric acid in an ice bath, and
extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over magnesium
sulfate. The solvent was removed, and the obtained residue was
washed with ether to obtain 38.9 mg (0.132 mmol, Yield: 37.2%) of
6-chloro-3-(2-methoxy-3,5,6-trimethylphenoxy)-4-pyridazinol
(Compound No. 1128).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 6.73 (1H, s), 6.67
(1H, s), 3.69 (3H, s), 2.29 (3H, s), 2.15 (3H, s),-2.09 (3H, s).
Melting point (.degree. C.): 209-210.
EXAMPLE 624
6-Chloro-3-[2-(1-isopropylvinyl)phenoxy]-4-pyridazinol (Compound
No. 2529) and
6-chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]-4-pyridazinol
(Compound No. 2542)
(1) 1-[2-(Methoxymethoxy)phenyl]ethanone
In N,N-dimethylformamide (25 mL) was dissolved 3.39 g (24.9 mmol)
of commercially available 1-(2-hydroxyphenyl)-ethanone, 1.52 g
(38.0 mmol) of 60% sodium hydride was added to the solution in an
ice bath, and the resulting mixture was stirred in an ice bath for
20 minutes. To the mixture was gradually added dropwise 3.00 mL
(39.5 mmol) of chloro(methoxy)methane, and the resulting mixture
was stirred at room temperature overnight. The reaction mixture was
poured into water, and extracted with ethyl acetate. The organic
layer was successively washed with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was removed, and the
obtained residue was purified by silica gel column chromatography
(Wako gel C-100, hexane-ethyl acetate, gradient) to obtain 4.33 g
(24.1 mmol, Yield: 96.8%) of
1-[2-(methoxymethoxy)phenyl]ethanone.
(2) 2-[2-(Methoxymethoxy)phenyl]-3-methyl-2-butanol
In dry tetrahydrofuran (3 mL) was dissolved 1.00 g (5.56 mmol) of
1-[2-(methoxymethoxy)phenyl]ethanone obtained in (1), and under
nitrogen atmosphere and ice-cooling, 2.8 mL (5.6 mmol) of a
tetrahydrofuran solution containing 2 mol/L isopropylmagnesium
bromide was added dropwise. After completion of dropwise addition,
the reaction mixture was stirred at room temperature for 1 hour and
30 minutes. The reaction mixture was poured into water, made acidic
with diluted hydrochloric acid, and then, extracted with ether. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
removed, and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate, gradient) to
obtain 0.522 g (2.33 mmol, Yield: 41.9%) of
2-[2-(methoxymethoxy)phenyl]-3-methyl-2-butanol.
(3) Mixture containing
6-chloro-3-[2-(1-isopropylvinyl)phenoxy]pyridazine 1-oxide and
6-chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]pyridazine 1-oxide,
etc.
In dichloromethane (3 mL) was dissolved 0.522 g (2.33 mmol) of
2-[2-(methoxymethoxy)phenyl]-3-methyl-2-butanol obtained in (2),
and in an ice bath, 0.50 mL (3.6 mmol) of triethylamine, then, 0.25
mL (3.2 mmol) of methanesulfonyl chloride were added to the
solution, and the resulting mixture was stirred at room temperature
overnight. The reaction mixture was poured into water, and
extracted with dichloromethane. The organic layer was successively
washed with water and brine, and dried over anhydrous magnesium
sulfate. The solvent was removed, and the residue was purified by
silica gel column chromatography (Wako gel C-100, hexane:ethyl
acetate, gradient) to obtain 186 mg of a crude product containing
2-(1,2-dimethyl-1-propenyl)phenol, etc. 132 mg of the crude product
was mixed with 1,4-dioxane (2 mL) and dimethylsulfoxide (2 mL), and
100 mg (0.893 mmol) of potassium tert-butoxide was added to the
mixture. Then, to the mixture was added 119 mg (0.721 mmol) of
3,6-dichloropyridazine 1-oxide, and the resulting mixture was
stirred at room temperature for 5 hours. The reaction mixture was
poured into water, and extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was removed,
and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane:ethyl acetate, gradient) to
obtain 220 mg of a mixture containing
6-chloro-3-[2-(1-isopropylvinyl)phenoxy]pyridazine 1-oxide and
6-chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]pyridazine 1-oxide,
etc.
(4) 4,6-Dichloro-3-[2-(1-isopropylvinyl)phenoxy]pyridazine and
4,6-dichloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]-pyridazine
(Step B-3)
In chloroform (0.4 mL) was dissolved 200 mg of a mixture containing
6-chloro-3-[2-(1-isopropylvinyl)phenoxy]pyridazine 1-oxide and
6-chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]pyridazine 1-oxide,
etc. obtained in (3), 0.40 mL (4.3 mmol) of phosphorus oxychloride
was mixed with the mixture and the resulting mixture was stirred at
70.degree. C. for 2 hours. The reaction mixture was poured into
water, and extracted with dichloromethane. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was distilled off and the
obtained residue was purified by preparative thin-layer
chromatography (available from MERCK CO., 1.05744, 3 plates were
used, developed by hexane:acetone =20:1 three times) to obtain 23
mg of 4,6-dichloro-3-[2-(1-isopropylvinyl)phenoxy]pyridazine
(purity 86%, containing 14% of
4,6-dichloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]pyridazine), and
50 mg of
4,6-dichloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]pyridazine
(purity 81%, containing 19% of
4,6-dichloro-3-[2-(1-isopropylvinyl)phenoxy]pyridazine).
(5) 6-Chloro-3-[2-(1-isopropylvinyl)phenoxy]-4-pyridazinol
(Compound No. 2529, Step A-3 and A-4)
In dimethylsulfoxide (1 mL) was dissolved 23 mg of
4,6-dichloro-3-[2-(1-isopropylvinyl)phenoxy]pyridazine (purity 86%,
containing 14% of
4,6-dichloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]pyridazine)
obtained in (4), 80 mg (0.98 mmol) of sodium acetate was added to
the solution and the mixture was stirred at 60.degree. C. for 9
hours. The reaction mixture was cooled, poured into water, and made
acidic with diluted hydrochloric acid. The mixture was extracted
with ethyl acetate, the organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 2 plates were used, developed
by hexane:ethyl acetate=1:1) to obtain 4.5 mg of
6-chloro-3-[2-(1-isopropylvinyl)phenoxy]-4-pyridazinol (Compound
No. 2529, purity 91%, containing 9%
6-chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]-4-pyridazinol).
Also, 11.0 mg of
6-chloro-3-[2-(1-isopropylvinyl)phenoxy]-4-pyridazinol (containing
23% 6-chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]-4-pyridazinol)
with a purity of 77% was obtained.
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.40-7.05 (4H, m),
6.59 (1H, s), 5.90 (1H, s), 5.04 (1H, s), 2.71 (1H, septet, J=6.9
Hz), 0.98 (6H, d, J=6.9 Hz). Appearance: amorphous.
(6) 6-Chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]-4-pyridazinol
(Compound No. 2542, Step A-3 and A-4)
In dimethylsulfoxide (2 mL) was dissolved 50 mg of
4,6-dichloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]-pyridazine
(purity 81%, containing 19% of
4,6-dichloro-3-[2-(1-isopropylvinyl)phenoxy]pyridazine) obtained in
(4), 68 mg (0.83 mmol) of sodium acetate was added to the solution
and the resulting mixture was stirred at 50.degree. C. for 11
hours. The reaction mixture was cooled, poured into water, and made
acidic with diluted hydrochloric acid. The mixture was extracted
with ethyl acetate, the organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 2 plates were used, developed
by hexane:ethyl acetate=2:1) to obtain 40.2 mg of
6-chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]-4-pyridazinol
(Compound No. 2542, purity 86%, containing 14% of
6-chloro-3-[2-(1-isopropylvinyl)phenoxy]-4-pyridazinol). Also, 3.7
mg of 6-chloro-3-[2-(1,2-dimethyl-1-propenyl)phenoxy]-4-pyridazinol
(containing 27% of
6-chloro-3-[2-(1-isopropylvinyl)phenoxy]-4-pyridazinol) with a
purity of 73% was obtained.
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.38-7.05 (4H, m),
6.59 (1H, s), 1.78 (3H, s), 1.62 (3H, s), 1.46 (3H, s). Appearance:
amorphous.
EXAMPLE 625
6-Chloro-3-[2-(2-methyl-1-propenyl)phenoxy]-4-pyridazinol (Compound
No. 2540)
(1) 1-(2-Methoxyphenyl)-2-methyl-1-propanol
Dry tetrahydrofuran (3 mL) was added to 1.01 g (7.43 mmol) of
commercially available 2-methoxybenzaldehyde under nitrogen
atmosphere, and the mixture was ice-cooled. To the mixture was
added dropwise a 3.8 mL (7.6 mmol) of tetrahydrofuran solution
containing 2 mol/L isopropyl-magnesium bromide. After completion of
dropwise addition, the reaction mixture was stirred in an ice bath
for 1 hour. The reaction mixture was poured into water, made acidic
with diluted hydrochloric acid, and then, extracted with ether. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
removed, and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate, gradient) to
obtain 1.00 g (5.56 mmol, Yield: 74.8%) of
1-(2-methoxyphenyl)-2-methyl-1-propanol.
(2) 1-(l-Chloro-2-methylpropyl)-2-methoxybenzene
In dichloromethane (3 mL) was dissolved 630 mg (3.50 mmol) of
1-(2-methoxyphenyl)-2-methyl-1-propanol obtained in (1), and then,
0.70 mL (5.0 mmol) of triethylamine, then 0.35 mL (4.5 mmol) of
methanesulfonyl chloride were added to the solution, and the
resulting mixture was stirred for 1 hour. The reaction mixture was
poured into water, and extracted with dichloromethane. The organic
layer was successively washed with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was removed to obtain 720
mg of 1-(1-chloro-2-methylpropyl)-2-methoxybenzene.
(3) 1-Methoxy-2-(2-methyl-1-propenyl)benzene
In dry N,N-dimethylformamide (8 mL) was dissolved 410 mg of
1-(1-chloro-2-methylpropyl)-2-methoxybenzene obtained in (2), and
to the solution was added 395 mg (3.52 mmol) of potassium
tert-butoxide in an ice bath. The reaction mixture was refluxed for
2 hours, then cooled to room temperature, and poured into water.
The mixture was extracted with hexane, the obtained organic layers
were combined, washed successively with water and brine. The
organic layer was dried over anhydrous magnesium sulfate, and the
solvent was removed to obtain 460 mg of
1-methoxy-2-(2-methyl-1-propenyl)benzene.
(4) 2-(2-Methyl-1-propenyl)phenol
Under nitrogen atmosphere, in dry N,N-dimethylformamide (3 mL) was
suspended 60.0 mg (1.50 mmol) of 60% sodium hydride, and to the
suspension was gradually added dropwise 0.11 mL (1.5 mmol) of
ethanethiol in an ice bath. After stirring for 10 minutes, a dry
N,N-dimethylformamide (0.5 mL) solution containing 200 mg of
1-methoxy-2-(2-methyl-1-propenyl)benzene obtained in (3) was added
dropwise to the mixture, and the resulting mixture was refluxed for
2 hours and 30 minutes. After allowing to stand for cooling, the
reaction mixture was poured into water, made acidic by adding
diluted hydrochloric acid, and extracted with hexane. The organic
layers were combined, washed successively with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was removed to
obtain 220 mg of 2-(2-methyl-1-propenyl)phenol.
(5) Mixture of
6-chloro-3-[2-(2-methyl-1-propenyl)phenoxy]-pyridazine 1-oxide and
3-chloro-6-[2-(2-methyl-1-propenyl)phenoxy]pyridazine 1-oxide (Step
B-2)
200 mg of 2-(2-methyl-1-propenyl)phenol obtained in (4),
1,4-dioxane (2 mL) and dimethylsulfoxide (2 mL) were mixed, 151 mg
(1.35 mmol) of potassium tert-butoxide was added to the mixture,
and the resulting mixture was stirred in an ice bath for 15
minutes. To the mixture was added 207 mg (1.25 mmol) of
3,6-dichloropyridazine 1-oxide, and the mixture was stirred in an
ice bath for 15 minutes, and then, at room temperature for 4 hours.
The reaction mixture was poured into water, and extracted with
ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane-ethyl acetate, gradient) to obtain 90.0 mg (0.325
mmol, Yield from 1-(2-methoxyphenyl)-2-methyl-1-propanol: 41.2%) of
a mixture of 6-chloro-3-[2-(2-methyl-1-propenyl)phenoxy]pyridazine
1-oxide and 3-chloro-6-[2-(2-methyl-1-propenyl)phenoxy]-pyridazine
1-oxide.
(6) 4,6-Dichloro-3-[2-(2-methyl-1-propenyl)phenoxy]-pyridazine
(Step B-3)
In chloroform (0.2 mL) was dissolved 90.0 mg (0.325 mmol) of a
mixture of 6-chloro-3-[2-(2-methyl-1-propenyl)phenoxy]pyridazine
1-oxide and 3-chloro-6-[2-(2-methyl-1-propenyl)phenoxy]pyridazine
1-oxide obtained in (5), 0.20 mL (2.2 mmol) of phosphorus
oxychloride was mixed with the above mixture, and the resulting
mixture was stirred at 70.degree. C. for 2 hours. The reaction
mixture was poured into water, extracted with dichloromethane. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 3
plates were used, developed by hexane:ethyl acetate=9:1) to obtain
85.0 mg (0.288 mmol, Yield: 88.6%) of
4,6-dichloro-3-[2-(2-methyl-1-propenyl)phenoxy]pyridazine.
(7) 6-Chloro-3-[2-(2-methyl-1-propenyl)phenoxy]-4-pyridazinol
(Compound No. 2540, Step A-3 and A-4)
In dimethylsulfoxide (3 mL) was dissolved 85.0 mg (0.288 mmol) of
4,6-dichloro-3-[2-(2-methyl-1-propenyl)phenoxy]pyridazine obtained
in (6), 122 mg (1.49 mmol) of sodium acetate was added to the
solution and the resulting mixture was stirred at 120.degree. C.
for 2 hours. The reaction mixture was cooled up to room
temperature, poured into water, and made acidic with diluted
hydrochloric acid. The mixture was extracted with ethyl acetate,
and the organic layers were combined, washed successively with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 2 plates were used, developed by ethyl acetate) to obtain
39.6 mg (0.143 mmol, Yield: 49.7%) of
6-chloro-3-[2-(2-methyl-1-propenyl)phenoxy]-4-pyridazinol (Compound
No. 2540).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.35-7.15 (3H, m),
7.15-7.05 (1H, m), 6.65 (1H, s), 6.05 (1H, s), 1.76 (3H, s), 1.70
(3H, s). Melting point (.degree. C.): 149-152.
EXAMPLE 626
6-Chloro-3-(3-hydroxyphenoxy)-4-pyridazinol (Compound No. 2544)
(1) Mixture of
1-{3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-phenyl}ethanone and
1-{3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]phenyl}ethanone
306 mg (2.25 mmol) of 1-(3-hydroxyphenyl)ethanone, 1,4-dioxane (6
mL) and dimethylsulfoxide (6 mL) were mixed, 297 mg (2.65 mmol) of
potassium tert-butoxide was added to the mixture, and the resulting
mixture was stirred in an ice bath for 15 minutes. To the mixture
was added 342 mg (2.07 mmol) of 3,6-dichloropyridazine 1-oxide in
an ice bath, and the resulting mixture was stirred at room
temperature for 4 hours. The reaction mixture was poured into
water, and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was removed, and the
obtained residue was purified by silica gel column chromatography
(Wako gel C-100, hexane-ethyl acetate, gradient) to obtain 400 mg
(1.51 mmol, Yield: 72.9%) of a mixture of
1-{3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]phenyl}ethanone and
1-{3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]phenyl}ethanone.
(2) Mixture of 3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-phenyl
acetate and 3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]phenyl
acetate
In 3 mL of dichloromethane was dissolved was dissolved 400 mg (1.51
mmol) of a mixture of
1-{3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]phenyl}ethanone and
1-{3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]phenyl}ethanone obtained
in (1), a dichloromethane (3 mL) solution containing 1.1 g (purity
70-75%, 4.5-4.8 mmol) of m-chloroperbenzoic acid was added to the
solution, and the resulting mixture was stirred at room temperature
for 4 days. To the reaction mixture was added a saturated aqueous
sodium sulfite solution, and after stirring, the mixture was
extracted with ethyl acetate. The organic layer was successively
washed with water and brine, and dried over anhydrous sodium
sulfate. The solvent was removed, and the obtained residue was
purified by silica gel column chromatography (Wako gel C-100,
hexane-ethyl acetate, gradient) to obtain 330 mg of a mixture of
the starting material,
3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]phenyl acetate, and
3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]phenyl acetate. In
dichloromethane (3 mL) was dissolved 280 mg of the mixture, 1.1 g
(purity 70-75%, 4.5-4.8 mmol) of m-chloroperbenzoic acid was added
to the solution, and the resulting mixture was stirred at room
temperature overnight. The reaction mixture was poured into 10%
aqueous sodium sulfite solution, and extracted with
dichloromethane. The organic layer was washed with water, and dried
over anhydrous sodium sulfate. The solvent was removed, and the
obtained residue was washed with hexane to obtain 310 mg of a
mixture of 3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]phenyl acetate
and 3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]phenyl acetate.
(3) 3-[(4,6-Dichloro-3-pyridazinyl)oxy]phenyl acetate (Step
B-3)
With chloroform (0.4 mL) was mixed 310 mg of a mixture of
3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]phenyl acetate and
3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]phenyl acetate obtained in
(2), 0.40 mL (4.3 mmol) of phosphorus oxychloride was mixed with
the above mixture, and the resulting mixture was stirred at
70.degree. C. for 3 hours. The reaction mixture was poured into
water and after stirring, the mixture was extracted with
dichloromethane. The organic layers were combined, washed with
water, and dried over anhydrous magnesium sulfate. The solvent was
removed, and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate, gradient) to
obtain 46.0 mg (0.154 mmol, Yield from a mixture of
1-{3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-phenyl}ethanone and
1-{3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]phenyl}ethanone: 9.6%) of
3-[(4,6-dichloro-3-pyridazinyl)oxy]phenyl acetate.
(4) 6-Chloro-3-(3-hydroxyphenoxy)-4-pyridazinol (Compound No. 2544,
Step A-3 and A-4)
In dimethylsulfoxide (1 mL) was dissolved 40.0 mg (0.134 mmol) of
3-[(4,6-dichloro-3-pyridazinyl)oxy]phenyl acetate obtained in (3),
56.0 mg (0.683 mmol) of sodium acetate was added to the solution
and the resulting mixture was stirred at 120.degree. C. for 1 hour.
After cooling up to room temperature, the reaction mixture was
poured into 0.5 mol/L aqueous sodium hydroxide solution, and washed
with ethyl acetate. The aqueous layer was made acidic with 4 mol/L
hydrochloric acid, and extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine.
After drying over anhydrous magnesium sulfate, the solvent was
removed to obtain 30 mg (0.126 mmol, Yield: 94.0%) of
6-chloro-3-(3-hydroxyphenoxy)-4-pyridazinol (Compound No.
2544).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.25-7.10 (1H, m),
6.70-6.57 (4H, m). Melting point (.degree. C.): 248-251.
EXAMPLE 627
6-Chloro-3-(2-iodo-3-methoxyphenoxy)-4-pyridazinol (Compound No.
2551)
(1) 1-Methoxy-3-(methoxymethoxy)benzene
In N,N-dimethylformamide(50 mL) was dissolved 3.68 g (29.7 mmol) of
commercially available 3-methoxyphenol, 1.81 g (45.4 mmol) of 60%
sodium hydride was added to the solution in an ice bath, and the
resulting mixture was stirred in an ice bath for 20 minutes. To the
mixture was gradually added dropwise in an ice bath 4.05 mL (53.3
mmol) of chloro(methoxy)methane, and the resulting mixture was
stirred at room temperature overnight. To the reaction mixture was
added a saturated aqueous ammonium chloride solution, and the
mixture was extracted with ethyl acetate. The organic layer was
successively washed with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane-ethyl acetate, gradient) to obtain 4.81 g (28.6 mmol,
Yield: 96.3%) of 1-methoxy-3-(methoxymethoxy)benzene.
(2) 2-Iodo-1-methoxy-3-(methoxymethoxy)benzene
In dry ether (50 mL) was dissolved 3.70 g (22.0 mmol) of
1-methoxy-3-(methoxymethoxy)benzene obtained in (1), the solution
was cooled to -78.degree. C. under nitrogem atmosphere, and 5.60 mL
(37.2 mmol) of tetramethylethylenediamine, then, 22.0 mL (35.2
mmol) of n-butyl lithium-hexane solution (1.60 M) were added to the
solution. The resulting mixture was stirred at -78.degree. C. for
30 minutes, then at 0C for 30 minutes, and cooled to -78.degree.
C., 9.80 g (38.6 mmol) of iodine was added to the mixture. The
mixture was stirred at -78.degree. C. for 30 minutes, a saturated
aqueous ammonium chloride solution was added to the reaction
mixture, and the mixture was extracted with ethyl acetate. The
organic layer was washed with a saturated aqueous sodium
thiosulfate solution, and dried over anhydrous magnesium sulfate.
The solvent was removed to obtain 6.59 g of
2-iodo-1-methoxy-3-(methoxymethoxy)benzene.
(3) 2-Iodo-3-methoxyphenol
In methanol (70 mL) was dissolved 6.59 g of
2-iodo-1-methoxy-3-(methoxymethoxy)benzene obtained in (2), conc.
hydrochloric acid (0.18 mL) was added dropwise to the solution, and
the resulting mixture was stirred at 65.degree. C. for 1 hour and
15 minutes. Moreover, conc. hydrochloric acid (0.20 mL) was
additionally added thereto, and the resulting mixture was stirred
at 65.degree. C. for 2 hours and 40 minutes. The reaction mixture
was poured into water, and extracted with ethyl acetate. The
organic layer was washed with brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane-ethyl acetate, gradient) to obtain 4.61 g (18.4 mmol,
Yield from 1-methoxy-3-(methoxymethoxy)benzene: 83.6%) of
2-iodo-3-methoxyphenol.
(4) Mixture of 6-chloro-3-(2-iodo-3-methoxyphenoxy)pyridazine
1-oxide and 3-chloro-6-(2-iodo-3-methoxyphenoxy)pyridazine 1-oxide
(Step B-2)
298 mg (1.19 mmol) of 2-iodo-3-methoxyphenol obtained in (3),
1,4-dioxane (2.5 mL) and dimethylsulfoxide (2.5 mL) were mixed, 215
mg (1.92 mmol) of potassium tert-butoxide was added to the mixture,
and the resulting mixture was stirred in an ice bath for 10
minutes. To the mixture was added 196 mg (1.19 mmol) of
3,6-dichloropyridazine 1-oxide in an ice bath, and the resulting
mixture was stirred at at room temperature for 3 days. To the
reaction mixture was added a saturated aqueous ammonium chloride
solution, and the mixture was extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the obtained residue was purified by preparative
thin-layer chromatography (developed by hexane:ethyl acetate=3:1,
then, hexane:ethyl acetate=1:1) to obtain 324 mg (0.855 mmol,
Yield: 71.8%) of a mixture of
6-chloro-3-(2-iodo-3-methoxyphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-iodo-3-methoxyphenoxy)pyridazine 1-oxide.
(5) 4,6-Dichloro-3-(2-iodo-3-methoxyphenoxy)pyridazine (Step
B-3)
1.0 mL (1.1 mmol) of phosphorus oxychloride was added to 324 mg
(0.855 mmol) of a mixture of
6-chloro-3-(2-iodo-3-methoxyphenoxy)pyridazine 1-oxide and
3-chloro-6-(2-iodo-3-methoxyphenoxy)pyridazine 1-oxide obtained in
(4), and the resulting mixture was stirred at room temperature
overnight. The reaction mixture was poured into water, and
extracted with ethyl acetate. The organic layers were combined,
washed successively with a saturated aqueous sodium hydrogen
carbonate solution and brine, and dried over anhydrous magnesium
sulfate. The solvent was removed, and the residue was purified by
silica gel column chromatography (Wako gel C-100, hexane-ethyl
acetate=5:1) to obtain 225 mg (0.567 mmol, Yield: 66.3%) of
4,6-dichloro-3-(2-iodo-3-methoxyphenoxy)pyridazine.
(6) 6-Chloro-3-(2-iodo-3-methoxyphenoxy)-4-pyridazinol (Compound
No. 2551, Step A-3 and A-4)
In dimethylsulfoxide (2 mL) was dissolved 105 mg (0.264 mmol) of
4,6-dichloro-3-(2-iodo-3-methoxyphenoxy)-pyridazine obtained in
(5), 118 mg (1.44 mmol) of sodium acetate was added to the solution
and the resulting mixture was stirred at 120.degree. C. for 1 hour
and 30 minutes. After cooling the mixture up to room temperature, 4
mol/L hydrochloric acid was added to the reaction mixture, and the
mixture was extracted with ethyl acetate. The organic layers were
combined, and washed with brine. After drying over anhydrous
magnesium sulfate, the solvent was removed, and the obtained
residue was washed with isopropyl ether to obtain 51.2 mg (0.135
mmol, Yield: 51.1%) of
6-chloro-3-(2-iodo-3-methoxyphenoxy)-4-pyridazinol (Compound No.
2551).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.39 (1H, t, J=8.4
Hz), 6.84 (2H, br.t, J=8.4 Hz), 6.73 (1H, s), 3.90 (3H, s). Melting
point (.degree. C.): 231-234.
EXAMPLE 628
6-Chloro-3-{[7-(3-hydroxypropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]oxy}-4-
-pyridazinol (Compound No. 2555)
(1) 2-Iodo-3-methoxyphenyl trifluoromethanesulfonate
In dry dichloromethane was dissolved 3.75 g (15.0 mmol) of
2-iodo-3-methoxyphenol obtained in Example 627(3), and 7.28 mL
(90.0 mmol) of pyridine was added to the solution. The mixture was
cooled to -20.degree. C., 5.40 mL (32.2 mmol) of
trifluoromethanesulfonic anhydride was added thereto, and the
resulting mixture was stirred for 3 hours and 50 minutes. The
reaction mixture was poured into water, and extracted with
dichloromethane, then with ethyl acetate. The organic layers were
combined, washed successively with 4 mol/L hydrochloric acid, water
and brine, and dried over anhydrous magnesium sulfate. The solvent
was removed, and the residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate=10:1) to
obtain 5.52 g (14.5 mmol, Yield: 96.7%) of 2-iodo-3-methoxyphenyl
trifluoromethanesulfonate.
(2)
tert-Butyl[(8-methoxy-2,3,4,4a-tetrahydro-8bH-benzo-[3,4]cyclobuta[1,2-
-b]pyran-8b-yl)oxy]dimethylsilane
In dry tetrahydrofuran (15 mL) was dissolved 1.10 g (2.88 mmol) of
2-iodo-3-methoxyphenyl trifluoromethanesulfonate obtained in (1),
and 1.00 mL (4.37 mmol) of commercially available
tert-butyl(3,4-dihydro-2H-pyran-6-yloxy)dimethylsilane was added to
the solution under nitrogen atmosphere. The mixture was cooled to
-78.degree. C., 4.50 mL (7.20 mmol) of n-butyl lithium-hexane
solution (1.60 M) was added to the mixture and the resulting
mixture was stirred for 20 minutes. The reaction mixture was poured
into a buffer (prepared by dissolving 9.1 g of KH.sub.2PO.sub.4 and
4.3 g of Na.sub.2HPO.sub.4 in 1 L of water) with a pH of 7, and
extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the residue was
purified by silica gel column chromatography (Wako gel C-100,
hexane-ethyl acetate=50:1) to obtain 0.897 g (2.79 mmol, Yield:
96.9%) of tert-butyl[(8-methoxy-2,3,4,4a-tetrahydro-8bH
-benzo[3,4]cyclobuta[1,2-b]pyran-8b-yl)oxy]dimethylsilane.
(3)
8-(3-Hydroxypropyl)-5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-one
In acetonitrile (12 mL) was dissolved 897 mg (2.79 mmol) of
tert-butyl[(8-methoxy-2,3,4,4a-tetrahydro-8bH
-benzo[3,4]cyclobuta[1,2-b]pyran-8b-yl)oxy]dimethylsilane obtained
in (2), 0.30 mL (7.96-8.30 mmol) of 46-47% hydrofluoric acid
aqueous solution was added to the solution in an ice bath, and the
resulting mixture was stirred for 30 minutes. The reaction mixture
was poured into a saturated aqueous sodium hydrogen carbonate
solution, and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was removed, and the
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane-ethyl acetate=7:3) to obtain 446 mg (2.17 mmol,
Yield: 77.8%) of
8-(3-hydroxypropyl)-5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-one.
(4)
8-(3-Chloropropyl)-5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-one
In dichloromethane (22 mL) was dissolved 474 mg (2.30 mmol) of
8-(3-hydroxypropyl)-5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-one
obtained in (3), 467 mg (3.49 mmol) of N-chlorosuccinimide and 917
mg (3.5 mmol) of triphenylphosphine were added to the solution, and
the resulting mixture was stirred at room temperature for 1 hour.
The reaction mixture was poured into water, a saturated aqueous
sodium hydrogen carbonate solution was added thereto, and the
mixture was extracted with ethyl acetate. The organic layers were
combined, washed with brineand dried over anhydrous magnesium
sulfate. The solvent was removed, and the residue was purified by
silica gel column chromatography (Wako gel C-100, hexane-ethyl
acetate=20:1) to obtain 409 mg (1.82 mmol, Yield: 79.1%) of
8-(3-chloropropyl)-5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-one.
(5) 7-(3-Chloropropyl)-2-methoxybicyclo[4.2.0]octa-1,3,5-triene
Water (6 mL) was added to 111 mg (0.408 mmol) of mercury chloride
(HgCl.sub.2) to dissolve therein, 4.00 g (6.12 mmol) of zinc powder
was added to the solution and the resulting mixture was stirred at
room temperature for 50 minutes. After removing the supernatant,
the remained solid was washed once with water. To the material were
gradually added water (6.0 mL), and then, conc. hydrochloric acid
(5.0 mL), and further added acetic acid (2.4 mL), and finally 409
mg (1.82 mmol) of
8-(3-chloropropyl)-5-methoxybicyclo[4.2.0]octa-1,3,5-trien-7-one
obtained in (4) dissolved in toluene (2 mL) and ethanol (2 mL). The
mixture was stirred at 115.degree. C. overnight, and cooled up to
room temperature. Toluene (20 mL) was added to the mixture and the
resulting mixture was stirred at 30 minutes, and the organic layer
was separated. The obtained organic layer was washed with water,
and dried over anhydrous magnesium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate=20:1) to
obtain 304 mg (1.44 mmol, Yield: 79.1%) of
7-(3-chloropropyl)-2-methoxybicyclo[4.2.0]octa-1,3,5-triene.
(6) 7-(3-Chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-ol
In dichloromethane(2.0 mL) was dissolved 304 mg (1.44 mmol) of
7-(3-chloropropyl)-2-methoxybicyclo[4.2.0]octa-1,3,5-triene
obtained in (5), 0.50 mL (5.32 mmol) of boron tribromide was added
to the solution in an ice bath with stirring, and the resulting
mixture was stirred in an ice bath for 1 hour. The reaction mixture
was poured into ice-water and extracted with ethyl acetate. The
organic layers were combined, washed with brineand dried over
anhydrous magnesium sulfate. The solvent was removed, and the
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane-ethyl acetate=4:1) to obtain 303 mg (1.54 mmol,
Yield: quantitative) of
7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-ol.
(7) Mixture of
6-chloro-3-{[7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]oxy}py-
ridazine 1-oxide and
3-chloro-6-{[7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]oxy}py-
ridazine 1-oxide (Step B-2)
303 mg (1.54 mmol) of
7-(3-chloropropyl)bicycle[4.2.0]octa-1,3,5-trien-2-ol obtained in
(6), 1,4-dioxane (2.0 mL) and dimethylsulfoxide (2.0 mL) were
mixed, 275 mg (2.46 mmol) of potassium tert-butoxide was added to
the mixture, and the resulting mixture was stirred in an ice bath
for 10 minutes. To the mixture was added 254 mg (1.54 mmol) of
3,6-dichloropyridazine 1-oxide in an ice bath, and the resulting
mixture was stirred at room temperature overnight. To the reaction
mixture was added a saturated aqueous ammonium chloride solution,
and the mixture was extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was distilled
off and the obtained residue was purified by preparative thin-layer
chromatography (developed by hexane:ethyl acetate=3:1) to obtain
364 mg (1.12 mmol, Yield: 72.7%) of a mixture of
6-chloro-3-{[7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]oxy}py-
ridazine 1-oxide and
3-chloro-6-{[7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]oxy}py-
ridazine 1-oxide.
(8)
4,6-Dichloro-3-{[7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl-
]oxy}pyridazine (Step B-3)
1.0 mL (11 mmol) of phosphorus oxychloride was added to 364 mg
(1.12 mmol) of a mixture of
6-chloro-3-{[7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]oxy}py-
ridazine 1-oxide and
3-chloro-6-{[7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]oxy}py-
ridazine 1-oxide obtained in (7), and the resulting mixture was
stirred at room temperature for 7 hours and 15 minutes. The
reaction mixture was poured into water, and extracted with ethyl
acetate. The organic layers were combined, washed successively with
a saturated aqueous sodium hydrogen carbonate solution and brine,
and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the residue was purified by preparative
thin-layer chromatography (developed by hexane:ethyl acetate=2:1)
to obtain 253 mg (0.735 mmol, Yield: 65.6%) of
4,6-dichloro-3-{[7-(3-chloropropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]ox-
y}pyridazine.
(9)
6-Chloro-3-{[7-(3-hydroxypropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]ox-
y}-4-pyridazinol (Compound No. 2555, Step A-3 and A-4)
In dimethylsulfoxide (5.0 mL) was dissolved 253 mg (0.735 mmol) of
4,6-dichloro-3-{[7-(3-chloropropyl)bicycle[4.2.0]octa-1,3,5-trien-2-yl]ox-
y}pyridazine obtained in (8), 250 mg (3.05 mmol) of sodium acetate
was added to the solution and the resulting mixture was stirred at
120.degree. C. for 2 hours. After cooling up to room temperature, 4
mol/L hydrochloric acid was added to the reaction mixture, and the
mixture was extracted with ethyl acetate. The organic layers were
combined, and washed with brine. After drying over anhydrous
magnesium sulfate, the solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(developed by hexane:ethyl acetate=2:1) to obtain 48.5 mg (0.158
mmol, Yield: 21.5%) of
6-chloro-3-{[7-(3-hydroxypropyl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl]oxy}--
4-pyridazinol (Compound No. 2555). Also, 28.2 mg of a mixture of
6-chloro-3-{[7-(3-chloropropyl)bicycle[4.2.0]octa-1,3,5-trien-2-yl]oxy}-4-
-pyridazinol and
3-{2-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]bicyclo[4.2.0]octa-1,3,5-trie-
n-7-yl}propyl acetate was obtained.
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.22-7.18 (1H, m),
6.98-6.94 (2H, m), 6.70 (1H, s), 3.62-3.56 (2H, m), 3.46 (1H,
br.s), 3.34 (1H, br.s), 3.18 (1H, dd, J=13.9, 5.5 Hz), 2.62 (1H,
dd, J=13.9, 2.2 Hz), 1.81-1.62 (4H, m). Appearance: oily
product.
EXAMPLE 629
6-Chloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]-4-pyrida-
zinol (Compound No. 2556)
(1) 5-Methoxy-8,8-dimethylbicyclo[4.2.0]octa-1,3,5-trien-7-one
In dry tetrahydrofuran(10 mL) was dissolved 723 mg (1.89 mmol) of
2-iodo-3-methoxyphenyl trifluoromethanesulfonate obtainable by the
method of Example 628(1), and 0.50 mL (2.47 mmol) of commercially
available [(1-methoxy-2-methyl-1-propynyl)oxy](trimethyl)silane was
added to the solution under nitrogen atmosphere. The mixture was
cooled to -78.degree. C., 2.70 mL (4.32 mmol) of n-butyl
lithium-hexane solution (1.60M) was added thereto and the resulting
mixture was stirred for 20 minutes. The reaction mixture was poured
into a buffer (prepared by dissolving 9.1 g of KH.sub.2PO.sub.4 and
4.3 g of Na.sub.2HPO.sub.4 in 1 L of water) with a pH of 7, and
extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and to the residue were
added tetrahydrofuran (2.0 mL), water (0.2 mL) and acetic acid (2.0
mL), and the resulting mixture was stirred at room temperature for
1 hour. Ether was added to the reaction mixture, and the mixture
was washed successively with a saturated aqueous sodium hydrogen
carbonate solution and brine, and dried over anhydrous magnesium
sulfate. The solvent was distilled off and the residue was purified
by preparative thin-layer chromatography (developed by hexane:ethyl
acetate=2:1) to obtain 182 mg (1.03 mmol, Yield: 54.5%) of
5-methoxy-8,8-dimethylbicyclo[4.2.0]octa-1,3,5-trien-7-one.
(2) 2-Methoxy-7,7-dimethylbicyclo[4.2.0]octa-1,3,5-triene
Water (6 mL) was added to 109 mg (0.401 mmol) of mercury chloride
(HgCl.sub.2) to dissolve therein, 3.98 g (6.09 mmol) of zinc powder
was added thereto and the resulting mixture was stirred at room
temperature for 1 hour. The supernatant was removed, and the
remained solid was washed once with water. To the material were
gradually added water (6.0 mL), then conc. hydrochloric acid (5.0
mL), and further acetic acid(2.4 mL), and finally 182 mg (1.03
mmol) of 5-methoxy-8,8-dimethylbicyclo[4.2.0]octa-1,3,5-trien-7-one
obtained in (1) dissolved in toluene (2 mL) and ethanol (2 mL). The
resulting mixture was stirred at 115.degree. C. over-night, and
cooled up to room temperature. Toluene (20 mL) was added to the
mixture and the mixture was stirred for 20 minutes, and the organic
layer was separated. The obtained organic layer was washed with
water, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the residue was purified by preparative
thin-layer chromatography (developed by hexane:ethyl acetate=25:1)
to obtain 85.1 mg (0.525 mmol, Yield: 51.0%) of
2-methoxy-7,7-dimethylbicyclo[4.2.0]octa-1,3,5-triene.
(3) 7,7-Dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-ol
In dichloromethane(5.0 mL) was dissolved 85.1 mg (0.525 mmol) of
2-methoxy-7,7-dimethylbicyclo[4.2.0]octa-1,3,5-triene obtained in
(2), 0.20 mL (2.12 mmol) of boron tribromide was added to the
solution in an ice bath with stirring, and the resulting mixture
was stirred in an ice bath for 2 hours and 10 minutes. The reaction
mixture was poured into ice-water and extracted with ethyl acetate.
The organic layers were combined, washed successively with water
and brine, and dried over anhydrous magnesium sulfate. The solvent
was removed to obtain 97.6 mg of
7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-ol.
(4)
6-Chloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]pyrid-
azine 1-oxide and
3-chloro-6-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]pyridazi-
ne 1-oxide (Step B-2)
97.6 mg of 7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-ol obtained
in (3), 1,4-dioxane (1.5 mL) and dimethylsulfoxide (1.5 mL) were
mixed, 97.8 mg (0.873 mmol) of potassium tert-butoxide was added to
the solution, and the resulting mixture was stirred in an ice bath
for 10 minutes. To the mixture was added 90.2 mg (0.547 mmol) of
3,6-dichloropyridazine 1-oxide in an ice bath, and the mixture was
stirred at room temperature overnight. To the reaction mixture was
added a saturated aqueous ammonium chloride solution, and the
mixture was extracted with ethyl acetate. The organic layers were
combined, washed with brineand dried over anhydrous magnesium
sulfate. The solvent was distilled off and the obtained residue was
purified by preparative thin-layer chromatography (developed by
hexane:ethyl acetate=3:1 two times) to obtain 61.7 mg (0.223 mmol,
Yield from 2-methoxy-7,7-dimethylbicyclo[4.2.0]octa-1,3,5-triene:
42.5%) of a mixture of
6-chloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]pyridazi-
ne 1-oxide and
3-chloro-6-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]-pyridaz-
ine 1-oxide.
(5)
4,6-Dichloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]p-
yridazine(Step B-3)
0.50 mL (5.4 mmol) of phosphorus oxychloride was added to 61.7 mg
(0.223 mmol) of a mixture of
6-chloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]-pyridaz-
ine 1-oxide and
3-chloro-6-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]pyridazi-
ne 1-oxide obtained in (4), and the resulting mixture was stirred
at room temperature overnight. The reaction mixture was poured into
water, and extracted with ethyl acetate. The organic layers were
combined, washed successively with a saturated aqueous sodium
hydrogen carbonate solution and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the residue
was purified by preparative thin-layer chromatography (developed by
hexane:ethyl acetate=5:1) to obtain 43.7 mg (0.148 mmol, Yield:
66.4%) of
4,6-dichloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]pyri-
dazine.
(6)
6-Chloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]-4-py-
ridazinol (Compound No. 2556, Step A-3 and Step A-4)
In dimethylsulfoxide(2.0 mL) was dissolved 43.7 mg (0.148 mmol) of
4,6-dichloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]pyri-
dazine obtained in (5), 63.1 mg (0.770 mmol) of sodium acetate was
added to the solution and the resulting mixture was stirred at
120.degree. C. for 2 hours. After cooling up to room temperature, 4
mol/L hydrochloric acid was added to the reaction mixture, and
extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine. After drying over
anhydrous magnesium sulfate, the solvent was removed, and the
obtained residue was washed with isopropyl ether to obtain 31.6 mg
(0.114 mmol, Yield: 77.0%) of
6-chloro-3-[(7,7-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)oxy]-4-pyrid-
azinol (Compound No. 2556).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.26-7.19 (1H, m),
6.97-6.89 (2H, m), 6.71 (1H, s), 2.81 (2H, s), 1.41 (6H, s).
Melting point (.degree. C.): 197-199.
EXAMPLE 630
4-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-3-methylphenyl acetate
(Compound No. 2572)
(1) Mixture of
1-{4-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-3-methylphenyl}ethanone
and
1-{4-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-3-methylphenyl}ethanone
(Step B-2)
784 mg (5.23 mmol) of commercially available
1-(4-hydroxy-3-methylphenyl)ethanone, 1,4-dioxane (5 mL) and
dimethylsulfoxide (5 mL) were mixed, 938 mg (8.38 mmol) of
potassium tert-butoxide was added to the mixture and the resulting
mixture was stirred in an ice bath for 10 minutes. To the mixture
was added 861 mg (5.22 mmol) of 3,6-dichloropyridazine 1-oxide in
an ice bath, and the mixture was stirred at room temperature
overnight. To the reaction mixture was added a saturated aqueous
ammonium chloride solution, and the mixture was extracted with
ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the residue was
purified by silica gel column chromatography (Wako gel C-100,
hexane-ethyl acetate=5:1) to obtain 758 mg (2.74 mmol, Yield:
52.5%) of a mixture of
1-{4-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-3-methylphenyl}ethanone
and
1-{4-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-3-methylphenyl}ethanone.
(2) Mixture of
4-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-3-methylphenyl acetate and
4-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-3-methylphenyl acetate
In 1,2-dichloroethane (13 mL) was dissolved 758 mg (2.74 mmol) of a
mixture of
1-{4-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-3-methylphenyl}ethanone
and
1-{4-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-3-methylphenyl}ethanone
obtained in (1), a dichloromethane (3 mL) solution containing 1.1 g
(purity 70-75%, 4.5-4.8 mmol) of m-chloroperbenzoic acid was added
to the solution, and the resulting mixture was stirred at room
temperature for 4 hours and 45 minutes. Moreover, 1.20 g (purity
70-75%, 4.86-5.20 mmol) of m-chloroperbenzoic acid was added to the
mixture, and the mixture was stirred at room temperature overnight.
The reaction mixture was poured into 10% aqueous sodium sulfite
solution, and extracted with ethyl acetate. The organic layer was
washed successively with a saturated aqueous sodium carbonate and
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (Wako gel C-100, hexane-ethyl acetate=5:1) to obtain
the starting material and 330 mg of a mixture of
3-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-phenyl acetate and
3-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-phenyl acetate. In
dichloromethane (3 mL) was dissolved 280 mg of the mixture, 2.62 g
(purity 70-75%, 10.6-11.4 mmol) of m-chloroperbenzoic acid was
added to the solution, and the resulting mixture was stirred at
room temperature for 4 hours and 45 minutes. Moreover, 1.20 g
(purity 70-75%, 4.86-5.20 mmol) of m-chloroperbenzoic acid was
added to the mixture, and the mixture was stirred at room
temperature overnight. The reaction mixture was poured into 10%
aqueous sodium sulfite solution, and extracted with ethyl acetate.
The organic layer was washed successively with a saturated aqueous
sodium carbonate and a saturated saline solution, and dried over
anhydrous sodium sulfate. The solvent was removed, and the residue
was purified by silica gel column chromatography (Wako gel C-100,
hexane-ethyl acetate=5:1) to obtain the starting material and 622
mg of a mixture of
4-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-3-methylphenyl acetate and
4-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-3-methylphenyl acetate. 0.5
mL (4.85 mmol) of 30% hydrogen peroxide aqueous solution was mixed
with 1,2-dichloroethane (2.2 mL), 3.2 mL (22.7 mmol) of
trifluoroacetic anhydride was added dropwise thereto in an ice
bath, and the resulting mixture was stirred at room temperature. In
an ice bath, this mixture was added to the mixture of the starting
material, 4-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-3-methylphenyl
acetate, and 4-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-3-methylphenyl
acetate, which was previously obtained and dissolved in
1,2-dichloroethane (2.2 mL), and the resulting mixture was stirred
in an ice bath for 1 hour, and at room temperature overnight. The
reaction mixture was poured into 10% aqueous sodium sulfite
solution, and extracted with ethyl acetate. The organic layer was
washed successively with a saturated aqueous sodium carbonate,
water and brine, and dried over anhydrous sodium sulfate. The
solvent was removed, and the residue was purified by silica gel
column chromatography (Wako gel C-100, hexane-ethyl acetate
gradient) to obtain 413 mg (1.40 mmol, Yield: 51.1%) of a mixture
of 4-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-3-methylphenyl acetate
and 4-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-3-methylphenyl
acetate.
(3) 4-[(4,6-Dichloro-3-pyridazinyl)oxy]-3-methylphenyl acetate
(Step B-3)
In chloroform(2 mL) was dissolved 413 mg (1.40 mmol) of a mixture
of 4-[(6-chloro-1-oxide-3-pyridazinyl)oxy]-3-methylphenyl acetate
and 4-[(6-chloro-2-oxide-3-pyridazinyl)oxy]-3-methylphenyl acetate
obtained in (2), 2.0 mL (22 mmol) of phosphorus oxychloride was
mixed with the solution, and the resulting mixture was stirred at
80.degree. C. for 3 hours. The reaction mixture was diluted with
dichloromethane, and then, poured into water. The mixture was
extracted with dichloromethane, and then, with ethyl acetate. The
organic layers were combined, washed successively with a saturated
aqueous sodium hydrogen carbonate solution and brine, and dried
over anhydrous magnesium sulfate. The solvent was removed, and the
obtained residue was purified by silica gel column chromatography
(Wako gel C-100, hexane-ethyl acetate, hexane-ethyl acetate=6:1) to
obtain 336 mg (1.07 mmol, Yield: 76.4%) of
4-[(4,6-dichloro-3-pyridazinyl)oxy]-3-methylphenyl acetate.
(4) 4-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]-3-methylphenyl
acetate (Compound No. 2572, Step A-3 and Step A-4)
In dimethylsulfoxide (1.5 mL) was dissolved 160 mg (0.511 mmol) of
4-[(4,6-dichloro-3-pyridazinyl)oxy]-3-methylphenyl acetate obtained
in (3), 136 mg (1.66 mmol) of sodium acetate was added to the
solution and the resulting mixture was stirred at 120.degree. C.
for 2 hours. After cooling up to room temperature, 4 mol/L
hydrochloric acid was added to the reaction mixture, and the
mixture was extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine. After drying
over anhydrous magnesium sulfate, the solvent was removed, and the
obtained residue was washed with isopropyl ether to obtain 37.3 mg
(0.126 mmol, Yield: 24.7%) of
4-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]-3-methylphenyl acetate
(Compound No. 2572).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.13-6.94 (3H, m),
6.70 (1H, s), 2.27 (3H, s), 2.17 (3H, s). Melting point (.degree.
C.): 255 (dec.).
EXAMPLE 631
6-Chloro-3-[2-(difluoromethyl)-6-methylphenoxy]-4-pyridazinol
(Compound No. 2576)
(1) 2-(methoxymethoxy)-3-methylbenzaldehyde
In N,N-dimethylformamide(50 mL) was dissolved 4.96 g (36.5 mmol) of
2-hydroxy-3-methylbenzaldehyde, 2.19 g (54.6 mmol) of 60% sodium
hydride was added to the solution in an ice bath and the resulting
mixture was stirred for 10 minutes. To the mixture was added 3.59
mL (47.3 mmol) of chloro(methoxy)methane in an ice bath, and the
resulting mixture was stirred at room temperature for 1 hour and 30
minutes. The reaction mixture was poured into a saturated aqueous
ammonium chloride solution, and extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the residue was purified by silica gel column
chromatography (Daisogel 1001W, hexane:ethyl acetate=50:1) to
obtain 6.60 g (36.6 mmol, Yield: 100%) of
2-(methoxymethoxy)-3-methylbenzaldehyde.
(2) 1-(Difluoromethyl)-2-(methoxymethoxy)-3-methylbenzene
In dichloromethane(10 mL) was dissolved 589 mg (3.27 mmol) of
2-(methoxymethoxy)-3-methylbenzaldehyde obtained in (1), 0.863 mL
(6.52 mmol) of (diethylamino)sulfur trifluoride (DAST) was added to
the solution under nitrogen atmosphere, and the resulting mixture
was stirred at room temperature for 3 hours. After allowing to
stand at room temperature overnight, the reaction mixture was
poured into water, and extracted with dichloromethane. The organic
layers were combined, washed with water, and dried over anhydrous
sodium sulfate. The solvent was removed, and the residue was
purified by silica gel column chromatography (Daisogel 1001W,
hexane:ethyl acetate=10:1) to obtain 229 mg (1.13 mmol, Yield:
34.6%) of
1-(difluoromethyl)-2-(methoxymethoxy)-3-methylbenzene.
(3) 2-(Difluoromethyl)-6-methylphenol
In methanol (5 mL) was dissolved 229 mg (1.13 mmol) of
1-(difluoromethyl)-2-(methoxymethoxy)-3-methylbenzene obtained in
(2), two drops of conc. hydrochloric acid was added to the solution
at room temperature and the resulting mixture was stirred at
60.degree. C. for 30 minutes. The reaction mixture was cooled to
room temperature, and the solvent was removed under reduced
pressure. Ethyl acetate was added to the residue, and the mixture
was washed with brineand dried over anhydrous sodium sulfate. The
solvent was removed to obtain 135 mg (0.854 mmol, Yield: 75.6%) of
2-(difluoromethyl)-6-methylphenol.
(4) 6-Chloro-3-[2-(difluoromethyl)-6-methylphenoxy]pyridazine
1-oxide and
3-chloro-6-[2-(difluoromethyl)-6-methylphenoxy]pyridazine 1-oxide
(Step B-1)
In 1,4-dioxane (1.5 mL) and dimethylsulfoxide (1.5 mL) was
dissolved 135 mg (0.854 mmol) of 2-(difluoromethyl)-6-methylphenol
obtained in (3), 115 mg (1.03 mmol) of potassium tert-butoxide was
added to the mixture in an ice bath, and the resulting mixture was
stirred for 5 minutes. To the mixture was added 141 mg (0.855 mmol)
of 3,6-dichloropyridazine 1-oxide in an ice bath, and the mixture
was stirred at room temperature overnight. The reaction mixture was
poured into water, and extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine, and
dried over anhydrous sodium sulfate. The solvent was removed, and
the obtained residue was purified by silica gel column
chromatography (eluted by hexane:ethyl acetate=2:1) and by
preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 3 plates were used, developed by hexane:ethyl acetate=2:1)
to obtain 28.6 mg (0.0997 mmol, Yield: 11.7%) of a mixture of
6-chloro-3-[2-(difluoromethyl)-6-methylphenoxy]pyridazine 1-oxide
and 3-chloro-6-[2-(difluoromethyl)-6-methylphenoxy]pyridazine
1-oxide.
(5)
4,6-Dichloro-3-[2-(difluoromethyl)-6-methylphenoxy]pyridazine(Step
B-3)
In chloroform(0.5 mL) was dissolved 28.6 mg (0.0997 mmol) of a
mixture of
6-chloro-3-[2-(difluoromethyl)-6-methylphenoxy]pyridazine 1-oxide
and 3-chloro-6-[2-(difluoromethyl)-6-methylphenoxy]pyridazine
1-oxide obtained in (4), 76.5 mg (0.50 mmol) of phosphorus
oxychloride was added to the solution and the resulting mixture was
refluxed for 8 hours. After allowing to stand at room temperature
overnight, water and dichloromethane were added to the reaction
mixture, and the resulting mixture was stirred for 30 minutes. The
mixture was extracted with dichloromethane, the organic layers were
combined, washed with water, and dried over anhydrous sodium
sulfate. The solvent was distilled off and the residue was purified
by preparative thin-layer chromatography (available from MERCK CO.,
1.05744, developed by hexane:ethyl acetate=4:1) to obtain 19.1 mg
(0.0626 mmol, Yield: 62.8%) of
4,6-dichloro-3-[2-(difluoromethyl)-6-methylphenoxy]pyridazine.
(6) 6-Chloro-3-[2-(difluoromethyl)-6-methylphenoxy]-4-pyridazinol
(Compound No. 2576)
In dimethylsulfoxide(0.5 mL) was dissolved 19.1 mg (0.0626 mmol) of
4,6-dichloro-3-[2-(difluoromethyl)-6-methylphenoxy]pyridazine
obtained in (5), 25.7 mg (0.313 mmol) of sodium acetate was added
to the solution and the resulting mixture was stirred at
120.degree. C. for 2 hours. After cooling up to room temperature,
water was added to the reaction mixture, and the mixture was
extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine. After drying over
anhydrous sodium sulfate, the solvent was distilled off and the
obtained residue was purified by preparative thin-layer
chromatography (available from MERCK CO., 1.05744, developed by
ethyl acetate) to obtain 17.8 mg (0.0620 mmol, Yield: 99.0%) of
6-chloro-3-[2-(difluoromethyl)-6-methylphenoxy-4-pyridazinol
(Compound No. 2576).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.55-7.25 (3H, m),
6.83 (1H, t, J=55.1 Hz). 2.15 (3H, s). Melting point (.degree. C.):
204-205.
EXAMPLE 632
6-Chloro-3-[2,4-dibromo-5-(ethylsulfanyl)phenoxy]-4-pyridazinol
(Compound No. 2596)
(1)
4,6-Dichloro-3-[2,4-dibromo-5-(ethylsulfanyl)phenoxy]pyridazine
2.05 g (8.84 mmol) of commercially available
1-bromo-2-methoxy-4-nitrobenzene and water (200 mL) were mixed, and
11.4 g (213 mmol) of ammonium chloride, then 4.78 g (73.2 mmol) of
zinc powder were added to the mixture. After stirring at room
temperature for 5 hours, the mixture was filtered through Celite,
and the filtrate was extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine, and
dried over anhydrous magnesium sulfate. The solvent was removed to
obtain 1.78 g of the residue.
The residue was mixed with water (9 mL) and 47% hydrobromic acid
aqueous solution (3 mL), an aqueous solution (3.6 mL of water)
containing 655 mg (9.49 mmol) of sodium nitrite was added dropwise
to the mixture in an ice bath with stirring. After completion of
the dropwise addition, the mixture was stirred for 10 minutes, and
973 mg (6.80 mmol) of cuprous bromide dissolved in 47% hydrobromic
acid aqueous solution (3.6 mL) was added dropwise to the mixture.
The reaction mixture was stirred at 110.degree. C. for 2 hours and
30 minutes, then cooled up to room temperature, water was added
thereto and the mixture was extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous magnesium sulfate. The solvent was
removed, and the obtained residue was purified by silica gel column
chromatography (Wako gel C-100, hexane: ethyl acetate=10:1) and by
preparative thin-layer chromatography (available from MERCK CO.,
1.05717, developed multiply by hexane:ethyl acetate=4:1) to obtain
751 mg of a crude product.
Under nitrogen atmosphere, in dry N,N-dimethylformamide (5 mL) was
suspended 339 mg (8.46 mmol) of 60% sodium hydride, and 0.65 mL
(8.78 mmol) of ethanethiol was gradually added dropwise to the
suspension. After stirring for 30 minutes, 751 mg of the previously
obtained crude product dissolved in N,N-dimethylformamide (8 mL)
was added to the mixture, and the resulting mixture was stirred at
160.degree. C. for 5 hours. After the reaction mixture was allowed
to stand at room temperature overnight, it was poured into water,
made acidic by adding diluted hydrochloric acid, and extracted with
ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 3 plates were used, developed
multiply by hexane:ethyl acetate=4:1) to obtain 109 mg of a
phenolic crude product.
109 mg of the obtained phenolic crude product was mixed with
1,4-dioxane (3 mL) and dimethylsulfoxide (3 mL), 53.5 mg (0.478
mmol) of potassium tert-butoxide was added to the mixture, and the
resulting mixture was stirred in an ice bath for 15 minutes. To the
mixture was added 71.2 mg (0.432 mmol) of 3,6-dichloropyridazine
1-oxide in an ice bath, and the resulting mixture was stirred at
room temperature overnight. The reaction mixture was poured into
water, and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was distilled off and the
obtained residue was purified by preparative thin-layer
chromatography (available from MERCK CO., 1.05744, 3 plates were
used, developed multiply by hexane:ethyl acetate=2:1) to obtain
71.5 mg of an etheric crude product.
In phosphorus oxychloride (3 mL) was dissolved 44.8 mg of the
etheric crude product, and the resulting mixture was stirred at
60.degree. C. for 21 hours. Water and dichloromethane were added to
the reaction mixture and after stirring, the mixture was extracted
with dichloromethane. The organic layers were combined, washed with
water, and dried over anhydrous magnesium sulfate. The solvent was
distilled off and the residue was purified by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 2
plates were used, developed by hexane:ethyl acetate=2:1) to obtain
14.4 mg (0.0314 mmol, Yield: 0.567%) of
4,6-dichloro-3-[2,4-dibromo-5-(ethylsulfanyl)phenoxy]pyridazine.
(2) 6-Chloro-3-[2,4-dibromo-5-(ethylsulfanyl)phenoxy]-4-pyridazinol
(Compound No. 2596, Step A-3 and A-4)
In dimethylsulfoxide (3 mL) was dissolved 33.4 mg (0.0728 mmol) of
4,6-dichloro-3-[2,4-dibromo-5-(ethylsulfanyl)phenoxy]pyridazine
obtained in (1), 29.8 mg (0.363 mmol) of sodium acetate was added
to the solution and the resulting mixture was stirred at
120.degree. C. for 4 hours and 30 minutes. After allowing to stand
at room temperature overnight, water was added to the reaction
mixture, the mixture was made acidic by adding diluted hydrochloric
acid, and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine. After drying
over anhydrous magnesium sulfate, the solvent was distilled off and
the obtained residue was purified by preparative thin-layer
chromatography (available from MERCK Co., 1.05744, developed
multiply by ethyl acetate) to obtain 13.1 mg (0.0297 mmol, Yield:
40.8%) of
6-chloro-3-[2,4-dibromo-5-(ethylsulfanyl)phenoxy]-4-pyridazinol
(Compound No. 2596).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.84 (1H, s), 7.21
(1H, s) 6.72 (1H, s), 2.97 (2H, q, J=7.3 Hz), 1.33 (3H, t, J=7.3
Hz). Melting point (.degree. C.): 225-228.
EXAMPLE 633
6-Chloro-3-(2,3,5-trimethyl-6-vinylphenoxy)-4-pyridazinol (Compound
No. 2603)
(1) 1-(2-Methoxy-3,4,6-trimethylphenyl)ethanone
In acetone (30 mL) was dissolved 2.00 g (11.2 mmol) of
1-(2-hydroxy-3,4,6-trimethylphenyl)ethanone which can be produced
by the method disclosed in Chemical Research in Toxicology, 1997,
vol. 10, No. 3, pp. 335-343, 3.10 g (22.4 mmol) of potassium
carbonate, then 1.40 mL (22.5 mmol) of methyl iodide were added to
the solution, and the resulting mixture was refluxed for 5 hours.
After cooling to room temperature, the reaction mixture was
concentrated, and the residue was poured into water, and extracted
with ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the residue was
purified by silica gel column chromatography (Wako gel C-100,
hexane:ethyl acetate gradient) to obtain 1.90 g (9.90 mmol, Yield:
88.4%) of 1-(2-methoxy-3,4,6-trimethylphenyl)ethanone.
(2) 1-(2-Methoxy-3,4,6-trimethylphenyl)ethanol
In methanol (8 mL) was dissolved 1.00 g (5.21 mmol) of
1-(2-methoxy-3,4,6-trimethylphenyl)ethanone obtained in (1), and
170 mg (4.50 mmol) of sodium borohydride was added to the solution
little by little with stirring. After confirmation of disappearance
of the starting materials by thin layer chromatography (TLC) for
analysis, the reaction mixture was poured into water, and made
acidic by adding hydrochloric acid. The mixture was extracted with
hexane, the organic layers were combined, washed successively with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was removed to obtain 1.0 g of
1-(2-methoxy-3,4,6-trimethylphenyl)ethanol.
(3) 2-(l-Chloroethyl)-3-methoxy-1,4,5-trimethylbenzene
In dichloromethane(10 mL) was dissolved 1.0 g of
1-(2-methoxy-3,4,6-trimethylphenyl)ethanol obtained in (2), and
1.10 mL (7.91 mmol) of triethylamine, then, 0.56 mL (7.21 mmol) of
methanesulfonyl chloride were added to the solution in an ice bath
with stirring. The reaction mixture was stirred at room temperature
for 20 minutes, poured into water, and extracted with
dichloromethane. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed to obtain 1.2 g of
2-(1-chloroethyl)-3-methoxy-1,4,5-trimethylbenzene.
(4) 3-Methoxy-1,2,5-trimethyl-4-vinylbenzene
In dry N,N-dimethylformamide (12 mL) was dissolved 1.2 g of
2-(1-chloroethyl)-3-methoxy-1,4,5-trimethylbenzene obtained in (3),
and 1.14 g (10.2 mmol) of potassium tertbutoxide was added to the
solution in an ice bath with stirring. The reaction mixture was
stirred at room temperature for 30 minutes, then, under reflux for
30 minutes. After cooling to room temperature, the mixture was
poured into water, and extracted with hexane. The organic layers
were combined, washed successively with water and brine, and dried
over anhydrous magnesium sulfate. The solvent was removed to obtain
870 mg of 3-methoxy-1,2,5-trimethyl-4-vinylbenzene.
(5) 2,3,5-Trimethyl-6-vinylphenol and
2-[1-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenol
Under nitrogen atmosphere, in dry N,N-dimethylformamide (8 mL) was
suspended 270 mg (6.75 mmol) of 60% sodium hydride, and 0.60 mL
(8.10 mmol) of ethanethiol was gradually added dropwise to the
suspension. After stirring for 15 minutes, 400 mg (2.27 mmol) of
3-methoxy-1,2,5-trimethyl-4-vinylbenzene obtained in (4) and
dissolved in dry N,N-dimethylformamide (1.5 mL) was added to the
mixture, and the resulting mixture was refluxed for 1 hour. After
cooling to room temperature, the reaction mixture was poured into
water, made acidic by adding hydrochloric acid, and extracted with
hexane. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was removed, and the residue was purified by silica gel
column chromatography (Wako gel C-100, hexane:ethyl acetate=20:1)
and by preparative thin-layer chromatography (available from MERCK
CO., 1.05744, developed by hexane:ethyl acetate=8:1) to obtain 63.0
mg (0.389 mmol, Yield from
1-(2-methoxy-3,4,6-trimethylphenyl)ethanone: 16.2%) of
2,3,5-trimethyl-6-vinylphenol and 330 mg (1.47 mmol, Yield from
1-(2-methoxy-3,4,6-trimethylphenyl)ethanone: 61.4%) of
2-[1-(ethylsulfanylethyl]-3,5,6-trimethylphenol.
(6) Mixture of
6-chloro-3-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine 1-oxide (Step
B-2)
In 1,4-dioxane (0.4 mL) and dimethylsulfoxide (0.4 mL) was
dissolved 43.0 mg (0.265 mmol) of 2,3,5-trimethyl-6-vinylphenol
obtained in (5), 36.0 mg (0.321 mmol) of potassium tert-butoxide
was added to the mixture in an ice bath, and the resulting mixture
was stirred for 10 minutes. To the mixture was added 47.6 mg (0.288
mmol) of 3,6-dichloropyridazine 1-oxide in an ice bath, and the
mixture was stirred at room temperature for 4 hours. The reaction
mixture was poured into water, and extracted with ethyl acetate.
The organic layers were combined, washed successively with water
and brine, and dried over anhydrous magnesium sulfate. The solvent
was distilled off and the obtained residue was purified by
preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 2 plates were used, developed by hexane:ethyl acetate=2:1)
to obtain 27.6 mg (0.0949 mmol, Yield: 35.8%) of a mixture of
6-chloro-3-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine 1-oxide.
(7) 4,6-Dichloro-3-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine (Step
B-3)
0.02 mL (0.22 mmol) of phosphorus oxychloride was added to 27.6 mg
(0.0949 mmol) of a mixture of
6-chloro-3-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine 1-oxide and
3-chloro-6-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine 1-oxide
obtained in (6), and the resulting mixture was stirred at room
temperature for 2 hours. To the mixture was added 0.4 mL of
chloroform, and the resulting mixture was stirred at room
temperature overnight. The reaction mixture was concentrated, 0.2
mL (2.2 mmol) of phosphorus oxychloride was added to the residue
and the resulting mixture was stirred at room temperature for 5
hours. The reaction mixture was concentrated, the residue was
purified by preparative thin-layer chromatography (available from
MERCK CO., 1.05744, 1 plate was used, developed by hexane:ethyl
acetate=5:1) to obtain 5.0 mg (0.016 mmol, Yield: 17%) of
4,6-dichloro-3-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine.
(8) 6-Chloro-3-(2,3,5-trimethyl-6-vinylphenoxy)-4-pyridazinol
(Compound No. 2603, Step A-3 and Step A-4)
In dimethylsulfoxide(1 mL) was dissolved 5.0 mg (0.016 mmol) of
4,6-dichloro-3-(2,3,5-trimethyl-6-vinylphenoxy)pyridazine obtained
in (7), 10.3 mg (0.126 mmol) of sodium acetate was added to the
solution and the resulting mixture was stirred at 120.degree. C.
for 2 hours. After cooling to room temperature, the reaction
mixture was poured into water, made acidic by adding hydrochloric
acid, and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine. After drying
over anhydrous magnesium sulfate, the solvent was distilled off and
the obtained residue was purified by preparative thin-layer
chromatography (available from MERCK CO., 1.05744, 1 plate was
used, developed by ethyl acetate) to obtain 1.5 mg (0.0052 mmol,
Yield: 33%) of
6-chloro-3-(2,3,5-trimethyl-6-vinylphenoxy)-4-pyridazinol (Compound
No. 2603).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.25 (1H, s), 6.67
(1H, dd, J=11.0 Hz, 17.6 Hz), 6.56 (1H, s), 5.66 (1H, dd, J=1.5 Hz,
17.6 Hz), 5.10 (1H, dd, J=1.5 Hz, 11.0 Hz), 2.29 (3H, s), 2.20 (3H,
s), 2.04 (3H, s). Appearance: amorphous.
EXAMPLE 634
6-Chloro-3-{2-[1-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenoxy}-4-pyridazin-
ol (Compound No. 2606)
(1)
6-Chloro-3-{2-[1-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenoxy}-4-metho-
xypyridazine(Step D-1)
In a mixed solvent of 1,4-dioxane (2 mL) and dimethylsulfoxide (2
mL) was dissolved 150 mg (0.670 mmol) of
2-[1-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenol obtained in
Example 633(5), 93 mg (0.83 mmol) of potassium tert-butoxide was
added to the solution in an ice bath, and the resulting mixture was
stirred at room temperature for 20 minutes. The mixture was again
cooled in an ice bath, 120 mg (0.670 mmol) of
3,6-dichloro-4-methoxypyridazine was added to the mixture, and the
resulting mixture was stirred at room temperature overnight. The
reaction mixture was poured into water, and extracted with ethyl
acetate. The organic layers were combined, washed successively with
water and brine, and dried over anhydrous magnesium sulfate. The
solvent was removed, and the obtained residue was purified by
silica gel chromatography (Wakogel C-100, hexane-ethyl acetate,
gradient) and by preparative thin-layer chromatography (available
from MERCK CO., 1.05744, 2 plates were used, developed by
hexane:ethyl acetate=2:1) to obtain 26.7 mg (0.0728 mmol, Yield:
10.9%) of
6-chloro-3-{2-[1-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenoxy}-4-methoxyp-
yridazine. Also, 60.0 mg (0.163 mmol, Yield: 24.3%) of
3-chloro-6-{2-[1-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenoxy}-4-methoxyp-
yridazine was obtained.
(2)
6-Chloro-3-{2-[l-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenoxy}-4-pyrid-
azinol (Compound No. 2606, Step D-2)
In dimethylsulfoxide (1 mL) was dissolved 34.0 mg (0.358 mmol) of
2-hydroxypyridine, 41.0 mg (0.366 mmol) of potassium tert-butoxide
was added to the solution at room temperature, and the resulting
mixture was stirred at room temperature for 20 minutes. To the
mixture was added a dimethylsulfoxide (1 mL) solution containing
26.7 mg (0.0728 mmol) of
6-chloro-3-{2-[1-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenoxy}-4-methoxyp-
yridazine obtained in (1), and the resulting mixture was stirred at
60.degree. C. After completion of the reaction, the reaction
mixture was allowed to stand for cooling, and poured into water.
After making the mixture acidic by adding hydrochloric acid to the
mixture, and the mixture was extracted with ethyl acetate. The
organic layers were combined, and washed successively with water
and brine. After drying over anhydrous magnesium sulfate, the
solvent was removed. The obtained residue was purified by
preparative thin-layer chromatography (available from Merck Co.,
1.05744, developed by ethyl acetate) to obtain 6.6 mg (0.019 mmol,
Yield: 26%) of
6-chloro-3-{2-[1-(ethylsulfanyl)ethyl]-3,5,6-trimethylphenoxy}-4-pyridazi-
nol (Compound No. 2606).
.sup.1H-NMR (200 MHz, CD.sub.3OD) 8 ppm: 7.20 (2H, s), 6.64 (1H,
s), 2.40-2.15 (8H, m), 2.03 (3H, s), 1.40 (3H, d, J=7.0 Hz), 1.24
(1H, m), 1.03 (3H, t, J=7.3 Hz). Appearance: amorphous.
EXAMPLE 635
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl phthalate
(Compound No. 1625) and
bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
phthalate (Compound No. 2838, Step I)
In acetonitrile (3 mL) was suspended 207 mg (0.726 mmol) of
(2,4-dichlorophenyl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)methanone,
81.6 mg (0.729 mmol) of 1,4-diazabicyclo[2.2.2]octane was added to
the suspension and the resulting mixture was stirred. To the
mixture was added 105 L (0.729 mmol) of phthaloyl dichloride, and
after stirring at room temperature for 1 hour, 200 mg (0.722 mmol)
of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol was
further added, and the resulting mixture was stirred at room
temperature for 1 hour and 30 minutes. The reaction mixture was
poured into ice-water, and extracted with ethyl acetate. The
organic layers were combined, washed successively with water and
brine, and dried over anhydrous sodium sulfate. The solvent was
removed, and the obtained residue was purified by silica gel column
chromatography (Daisogel 1001W, hexane:ethyl acetate, gradient) to
obtain 28.0 mg (0.0405 mmol, Yield: 5.61%) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl phthalate
(Compound No. 1625) and 163 mg (0.238 mmol, Yield: 33.0%) of
bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
phthalate (Compound No. 2838).
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl phthalate
(Compound No. 1625):
.sup.1H-NMR (200 MHz, CDCl.sub.3) 8 ppm: 8.01-7.96 (1H, m),
7.89-7.68 (3H, m), 7.57 (1H, s), 7.29-7.06 (5H, m), 6.90-6.83 (1H,
m), 3.71 (3H, s), 2.27 (3H, s), 2.13 (3H, s), 1.82-1.68 (1H, m),
0.77-0.53 (4H, m). Appearance: amorphous.
Bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
phthalate (Compound No. 2838):
.sup.1H-NMR (200 MHz, CDCl.sub.3) 8 ppm: 8.13-8.06 (2H, m),
7.84-7.78 (2H, m), 7.58 (2H, s), 7.15-7.06 (4H, m), 6.90-6.83 (2H,
m), 2.13 (6H, s), 1.82-1.68 (2H, m), 0.73-0.52 (8H, m). Appearance:
amorphous.
EXAMPLE 636
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl
1,3-benzenedisulfonate (Compound No. 2333) and
bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
1,3-benzenedisulfonate (Compound No. 3755, Step I)
In acetonitrile (4 mL) was suspended 122 mg (0.428 mmol) of
(2,4-dichlorophenyl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)methanone,
72.0 mg (0.643 mmol) of 1,4-diazabicyclo[2.2.2]octane, then 117 mg
(0.425 mmol) of 1,3-benzenedisulfonyl dichloride were added to the
suspension in an ice bath, and the resulting mixture was stirred at
room temperature for 30 minutes. The reaction mixture was
ice-cooled, and further 100 mg (0.361 mmol) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol was added
to the mixture, and the mixture was stirred at room temperature for
1 hour. The reaction mixture was poured into water, and extracted
with ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane:ethyl acetate, gradient) to obtain 135 mg (0.177
mmol, Yield: 49.0%) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl
1,3-benzenedisulfonate (Compound No. 2333) and 38.0 mg (0.0503
mmol, Yield: 13.9%) of
bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
1,3-benzenedisulfonate (Compound No. 3755).
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl
1,3-benzenedisulfonate (Compound No. 2333):
H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.67 (1H, t, J=1.9 Hz),
8.40-8.34 (1H, m), 8.31-8.24 (1H, m), 7.86 (1H, t, J=8.0 Hz), 7.56
(1H, s), 7.37 (1H, d, J=1.9 Hz), 7.29-7.23 (1H, m), 7.15-7.00 (3H,
m), 6.85-6.78 (1H, m), 3.81 (3H, s), 2.00 (3H, s), 1.94 (3H, s),
1.70-1.52 (1H, m), 0.73-0.45 (4H, m). Appearance: amorphous.
Bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
1,3-benzenedisulfonate (Compound No. 3755):
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.77 (1H, dd, J=1.8
Hz, 1.8 Hz), 8.41 (2H, dd, J=7.7 Hz, 1.8 Hz), 7.88 (1H, t, J=8.0
Hz), 7.48 (2H, s), 7.15-6.95 (4H, m), 6.90-6.75 (2H, m), 1.97 (6H,
s), 1.67-1.46 (2H, m), 0.75-0.44 (8H, m). Appearance:
amorphous.
EXAMPLE 637
Bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
pentanedioate (Compound No. 2746) and
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl pentanedioate
(Compound No. 2739)
In acetonitrile (8 mL) was suspended 241 mg (0.870 mmol) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol, in an ice
bath 139 mg (1.23 mmol) of 1,4-diazabicyclo[2.2.2]octane, then 146
mg (0.864 mmol) of pentanedioyl dichloride, and further 244 mg
(0.856 mmol) of
(2,4-dichlorophenyl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)methanone
were added to the suspension, and the resulting mixture was stirred
at room temperature. The reaction mixture was poured into water,
and extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane: ethyl acetate, gradient) and by preparative
thin-layer chromatography (available from MERCK CO., 1.05744, 2
plates were used, developed by hexane:ethyl acetate=2:1 or 1:1) to
obtain 42.0 mg (0.0646 mmol, Yield: 7.48%) of
bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
pentanedioate (Compound No. 2746) and 35.0 mg (0.0532 mmol, Yield:
6.21%) of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl pentanedioate
(Compound No. 2739).
Bis[6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl]
pentanedioate (Compound No. 2746):
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.23 (2H, s),
7.14-7.02 (4H, m), 6.83 (2H, dd, J=6.6, 2.9 Hz), 2.89 (4H, t, J=7.0
Hz), 2.25 (2H, quintet, J=7.0 Hz), 2.10 (6H, s), 1.80-1.65 (2H, m),
0.78-0.52 (8H, m). Appearance: caramel-like.
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
4-(2,4-dichlorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl pentanedioate
(Compound No. 2739):
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.45-7.17 (4H, m),
7.14-7.00 (2H, m), 6.90-6.75 (1H, m), 3.53 (3H, s), 2.83 (2H, t,
J=7.0 Hz), 2.57 (2H, t, J=7.0 Hz), 2.20-2.00 (2H, m), 2.11 (3H, s),
2.10 (3H, s), 1.80-1.65 (1H, m), 0.80-0.50 (4H, m). Appearance:
amorphous.
EXAMPLE 638
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-pyrrolidinecarboxylate (Compound No. 1937)
200 mg (0.722 mmol) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol was mixed
with toluene (3 mL) and the mixture was ice-cooled. To the mixture
were added 60 L (0.742 mmol) of pyridine, then 0.67 mL (0.724 mmol)
of 1.08 mol/L phosgene-toluene solution under nitrogen atmosphere
with stirring, and the resulting mixture was stirred at room
temperature for 15 minutes. The reaction mixture was ice-cooled, 60
L (0.722 mmol) of pyridine, then 60 L (0.719 mmol) of pyrrolidine
were added to the mixture, and the resulting mixture was stirred at
room temperature for 1 hour. The reaction mixture was poured into
water, and extracted with ethyl acetate. The organic layers were
combined, washed successively with water and brine, and dried over
anhydrous magnesium sulfate. The solvent was distilled off and the
obtained residue was purified by preparative thin-layer
chromatography (available from MERCK CO., 1.05744, 4 plates were
used, developed by hexane:ethyl acetate=2:1) to obtain 190 mg
(0.508 mmol, Yield: 70.7%) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
1-pyrrolidinecarboxylate (Compound No. 1937).
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.59 (1H, s),
7.15-7.03 (2H, m), 6.90-6.80 (1H, m), 3.62 (2H, dd, J=6.6 Hz, 6.9
Hz), 3.51 (2H, dd, J=6.9 Hz, 6.6 Hz), 2.15 (3H, s), 2.05-1.90 (4H,
m), 1.88-1.68 (1H, m), 0.80-0.50 (4H, m). Melting point (.degree.
C.): 115-118.
EXAMPLE 639
6-Chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
methoxy(methyl)carbamate (Compound No. 3564)
200 mg (0.722 mmol) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol was mixed
with toluene (3 mL) and the mixture was ice-cooled. To the mixture
were added 60 L (0.742 mmol) of pyridine, then 0.67 mL (0.724 mmol)
of 1.08 mol/L phosgene-toluene solution under nitrogen atmosphere
with stirring, and the resulting mixture was stirred at room
temperature for 15 minutes. The reaction mixture was ice-cooled,
120 L (1.48 mmol) of pyridine, then 70.4 mg (0.722 mmol) of
N,O-dimethylhydroxylamine hydrochloride were added to the mixture,
and the resulting mixture was stirred at room temperature for 1
hour. The reaction mixture was poured into water, and extracted
with ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel column chromatography (Wako gel
C-100, hexane: ethyl acetate, gradient) to obtain 100 mg (0.275
mmol, Yield: 38.1%) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
methoxy(methyl)carbamate (Compound No. 3564).
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 7.53 (1H, s),
7.15-7.03 (2H, m), 6.90-6.82 (1H, m), 3.84 (3H, s), 3.35 (3H, s),
2.15 (3H, s), 1.87-1.67 (1H, m), 0.80-0.52 (4H, m). Melting point
(.degree. C.): 63-64.5.
EXAMPLE 640
6-Chloro-3-(2-cyclopropyl-6-methylphen6xy)-4-pyridazinyl
2,5-dimethyl-1H-pyrrole-1-carboxylate (Compound No. 3630)
37.4 mg (0.393 mmol) of 2,5-dimethyl-1H-pyrrole was mixed with
toluene (1 mL), 40.0 L (0.407 mmol) of pyridine, then 0.34 mL
(0.367 mmol) of 1.08 mol/L phosgene-toluene solution were added to
the mixture in an ice bath with stirring, and the resulting mixture
was stirred for 1 hour. To the mixture were added 40.0 L (0.407
mmol) of pyridine, then 100 mg (0.361 mmol) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol, and the
resulting mixture was stirred for 3 hours. The reaction mixture was
poured into water, and extracted with ethyl acetate. The organic
layers were combined, washed with water, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the obtained
residue was purified by preparative thin-layer chromatography
(available from MERCK CO., 1.05744, 2 plates were used, developed
by hexane:ethyl acetate=2:1) to obtain 24.0 mg (0.0603 mmol, Yield:
16.7%) of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl
2,5-dimethyl-1H-pyrrole-1-carboxylate (Compound No. 3630).
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.20-8.03 (1H, m),
7.63 (1H, s), 7.13-7.00 (2H, m), 6.90-6.80 (1H, m), 6.36 (1H, d,
J=2.9 Hz), 2.55 (3H, s), 2.22 (3H, s), 2.15 (3H, s), 1.90-1.70 (1H,
m), 0.80-0.50 (4H, m). Melting point (.degree. C.): 208-210.
EXAMPLE 641
4-{[4-(benzoyloxy)-6-chloro-3-pyridazinyl]oxy}-3-methylphenyl
benzoate (Compound No. 3850)
(1) 6-Chloro-3-(4-hydroxy-2-methylphenoxy)-4-pyridazinol
In 1,4-dioxane(1.4 mL) was dissolved 173 mg (0.553 mmol) of
4-[(4,6-dichloro-3-pyridazinyl)oxy]-3-methylphenyl acetate obtained
in Example 630(3), 0.7 mL (2.1 mmol) of 3 mol/L sodium hydroxide
solution and dimethylsulfoxide (2.8 mL) were added to the solution
and the resulting mixture was stirred at room temperature
overnight. To the reaction mixture was added 4 mol/L hydrochloric
acid, and the mixture was extracted with ethyl acetate. The organic
layers were combined, washed successively with water and brine.
After drying over anhydrous magnesium sulfate, the solvent was
removed. The obtained residue was purified by preparative
thin-layer chromatography (developed by
dichloromethane:methanol=36:1) to obtain 66.8 mg of
6-chloro-3-(4-hydroxy-2-methylphenoxy)-4-pyridazinol.
(2) 4-{[4-(Benzoyloxy)-6-chloro-3-pyridazinyl]oxy}-3-methylphenyl
benzoate (Compound No. 3850)
In acetonitrile (1.0 mL) was dissolved 66.8 mg of
6-chloro-3-(4-hydroxy-2-methylphenoxy)-4-pyridazinol obtained in
(1), 60.0 mg (0.536 mmol) of 1,4-diazabicyclo[2.2.2]-octane, then,
61 L (0.523 mmol) of benzoyl chloride were added to the solution
and the resulting mixture was stirred at room temperature for 1
hour and 30 minutes. The reaction mixture was poured into water,
and extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine. After drying over
anhydrous magnesium sulfate, the solvent was removed. The obtained
residue was purified by preparative thin-layer chromatography
(developed by hexane:ethyl acetate=5:1) to obtain 36.9 mg (0.0800
mmol, Yield from 4-[(4,6-dichloro-3-pyridazinyl)oxy]-3-methylphenyl
acetate: 14.5%) of
4-{[4-(benzoyloxy)-6-chloro-3-pyridazinyl]oxy}-3-methylphenyl
benzoate (Compound No. 3850).
.sup.1H-NMR (200 MHz, CDCl.sub.3) .delta. ppm: 8.21-8.17 (4H, m),
7.72-7.48 (7H, m), 7.22-7.07 (3H, m), 2.21 (3H, s). Melting point
(.degree. C.): 118-120.
EXAMPLE 642
3-(2-Aminophenoxy)-3-chloro-4-pyridazinol (Compound No. 377)
(1) 2-[(6-chloro-4-methoxy-3-pyridazinyl)oxy]aniline(Step D-1)
In a mixed solvent of 1,4-dioxane (7 mL) and dimethylsulfoxide (7
mL) was dissolved 670 mg (6.15 mmol) of 2-aminophenol, 690 mg (6.16
mmol) of potassium tertbutoxide was added to the solution in an ice
bath and the resulting mixture was stirred for 10 minutes. To the
mixture was added 1000 mg (5.59 mmol) of
3,6-dichloro-4-methoxypyridazine, and the resulting mixture was
stirred at room temperature for 5 hours. The reaction mixture was
poured into ice water, and after adding brine, the mixture was
extracted with ethyl acetate. The organic layers were combined,
washed successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was removed, and the obtained
residue was purified by silica gel chromatography (Wakogel C-100,
hexane-ethyl acetate, gradient) to obtain 328 mg (1.30 mmol, Yield:
23.3%) of 2-[(6-chloro-4-methoxy-3-pyridazinyl)oxy]aniline and 100
mg of a mixture of 2-[(6-chloro-4-methoxy-3-pyridazinyl)oxy]aniline
and 2-[(6-chloro-5-methoxy-3-pyridazinyl)oxy]aniline.
(2) 3-(2-Aminophenoxy)-3-chloro-4-pyridazinol (Compound No. 377,
Step D-2)
In dimethylsulfoxide (0.4 mL) was dissolved 50.0 mg (0.198 mmol) of
2-[(6-chloro-4-methoxy-3-pyridazinyl)oxy]aniline obtained in (1),
(0.2 mL, 0.4 mmol) of 2 mol/L aqueous sodium hydroxide solution was
added to the solution and the resulting mixture was stirred at room
temperature for 5 hours. The reaction mixture was poured into
brine, and extracted with tetrahydrofuran. The organic layers were
combined, washed with brineand dried over anhydrous magnesium
sulfate. The solvent was distilled off and the residue was purified
by preparative thin-layer chromatography (available from MERCK CO.,
1.05744, 2 plates were used, developed by
dichloromethane:methanol=10:1) to obtain 17.0 mg (0.0714 mmol,
Yield: 36.1%) of 3-(2-aminophenoxy)-3-chloro-4-pyridazinol
(Compound No. 377).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.50-6.94 (2H, m),
6.90-6.82 (1H, m), 6.85-6.63 (2H, m). Melting point (.degree. C.):
249-250.
EXAMPLE 643
N-{2-[(6-Chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}acetamide
(Compound No. 380)
18.0 mg (0.0756 mmol) of 3-(2-aminophenoxy)-3-chloro-4-pyridazinol
obtained in Example 641 was mixed with dichloromethane (0.8 mL),
0.050 mL (0.36 mmol) of triethylamine, then 0.010 mL (0.14 mmol) of
acetyl chloride were added to the mixture in an ice bath with
stirring, and the resulting mixture was stirred at room temperature
for 3 hours. The reaction mixture was poured into brine, and
extracted with tetrahydrofuran. The organic layers were combined,
washed with brineand dried over anhydrous magnesium sulfate. The
solvent was distilled off and the residue was purified by
preparative thin-layer chromatography (available from MERCK CO.,
1.05715, developed by dichloromethane:methanol=10:1) to obtain 3.6
mg (0.0129 mmol, Yield: 17.1%) of
N-{2-[(6-chloro-4-hydroxy-3-pyridazinyl)oxy]phenyl}acetamide
(Compound No. 380).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 8.10-8.00 (1H, m),
7.25-7.08 (3H, m), 6.60 (1H, s), 2.12 (3H, s). Melting point
(.degree. C.): 135.
EXAMPLE 644
N,N,N-Tributyl-1-butanaminium
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinolate(Compound
No. 3798)
To an ethanol (2 mL) solution containing 105 mg (0.379 mmol) of
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol were added
0.19 mL (0.38 mmol) of 2 mol/L aqueous sodium hydroxide solution,
then, 106 mg (0.381 mmol) of tetrabutylammonium chloride, and the
resulting mixture was stirred at 60.degree. C. for 5 hours. The
reaction mixture was allowed to stand at room temperature
overnight, and the solid was removed by filtration. The filtrate
was concentrated to obtain N,N,N-tributyl-1-butanaminium
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinolate
(Compound No. 3798).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.05-6.95 (2H, m),
6.80-6.73 (1H, m), 6.43 (1H, s), 3.30-3.15 (8H, m), 2.14 (3H, s),
2.00-1.85 (1H, m), 1.76-1.53 (8H, m), 1.50-1.30 (8H, m), 1.02 (9H,
t, J=7.1 Hz), 0.78-0.63 (2H, m), 0.63-0.48 (2H, m). Melting point
(.degree. C.): 113-114.
EXAMPLE 645
Sodium 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinolate
(Compound No. 3805)
0.18 mL (0.36 mmol) of 2 mol/L aqueous sodium hydroxide solution
was added to an ethanol (2 mL) solution containing 100 mg (0.361
mmol) of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol,
and the resulting mixture was stirred at 50.degree. C. for 4 hours.
The reaction mixture was concentrated to obtain 108 mg (0.361 mmol,
Yield: 100%) of sodium
6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinolate
(Compound No. 3805).
.sup.1H-NMR (200 MHz, CD.sub.3OD) 8 ppm: 7.05-6.95 (2H, m), 6.77
(1H, dd,J=6.4, 3.1 Hz), 6.43 (1H, s), 2.14 (3H, s), 2.00-1.82 (1H,
m), 0.78-0.63 (2H, m), 0.63-0.48 (2H, m). Melting point (.degree.
C.): >260.
EXAMPLE 646
5-Bromo-6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol
(Compound No. 3843)
108 mg (0.607 mmol) of N-bromosuccinimide was added to a
N,N-dimethylformamide (2 mL) solution containing 157 mg (0.567
mmol) of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol,
and the resulting mixture was stirred at room temperature for 3
hours and 30 minutes. Water, and then, 4 mol/L hydrochloric acid
were added to the reaction mixture, and the mixture was extracted
with ethyl acetate. The organic layers were combined, washed
successively with water and brine, and dried over anhydrous
magnesium sulfate. The solvent was distilled off and the residue
was purified by preparative thin-layer chromatography (available
from MERCK CO. 1.05744, developed by hexane:ethyl acetate=2:1) to
obtain 123 mg (0.346 mmol, Yield: 61.0%) of
5-bromo-6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol
(Compound No. 3843).
.sup.1H-NMR (200 MHz, CD.sub.3OD) .delta. ppm: 7.08-7.05 (2H, m),
6.85-6.80 (1H, m), 2.14 (3H, s), 1.88-1.76 (1H, m), 0.82-0.72 (2H,
m), 0.60-0.56 (2H, m). Appearance: amorphous.
Compounds of Compounds Nos. 1 and 6 can be produced in accordance
with the method of Example 2.
Compounds of Compounds Nos. 123-127, 130-138, 144, 145, 151, 163,
173, 184, 202, 217, 226, 249, 264, 265, 266, 267, 269-275, 279,
280, 284, 287, 288, 292, 293, 300, 304, 305, 306, 307, 308, 309,
311, 315, 324, 325, 329, 330, 334, 336, 339, 344, 348, 349, 355,
356, 359, 361, 362, 364-370, 375, 376, 379, 383, 385-387, 390, 391,
396, 399-401, 403, 410, 412, 413, 415-425, 426, 427, 430, 432-438,
441, 443, 446, 450, 453, 454, 456, 458-460, 472, 491, 498, 503,
505, 506, 507, 510, 513, 514, 520, 521, 527-529, 531, 532, 534-536,
538-541, 544, 547, 549, 552, 556, 557, 558, 559, 562, 566, 567,
571, 614, 618, 621, 623, 626-629, 635, 640, 642, 650, 653, 658,
659, 662-664, 667, 679, 680, 692, 700, 701, 702, 707-712, 716,
71.7, 719, 731-733, 734, 735-737, 740, 746, 754, 756, 758, 759,
762, 775, 778, 780-782, 802-804, 834, 844-846, 850, 890, 894, 896,
911, 914, 931, 964, 965, 979, 982, 987, 998, 1000, 1007, 1009,
1013, 1016, 1020, 1023, 1027, 1040, 1050, 1052, 1053, 1055, 1058,
1060, 1061, 1063, 1064, 1066, 1069, 1073, 1080, 1083, 1086, 1088,
1089, 1091, 1096, 1099, 1100, 1102, 1115, 1118-1120, 1122-1125,
1129, 1133, 2519, 2547, 2548, 2565, 2568, 2570, 2571, 2574, 2577,
2585, 2587, 2589, 2592, 2597, 2599, 2600, 2601, 2605, 2607, 2608,
2609 and 2614 can be produced in accordance with the method of
Example 1, Example 6, Example 13, Example 16, Example 21, Example
22 or Example 23.
Compounds of Compound No. 1140, 1151, 1160, 1172, 1178, 1184, 1207,
1251, 1260, 1266, 1286, 1298, 1334, 1340, 1358, 1364, 1382, 1387,
1391, 1396, 1417, 1441, 1446, 1448, 1450, 1455-1459, 1461, 1481,
1509, 1522, 1531, 1537, 1543, 1549, 1553, 1554, 1566, 1575, 1593,
1599, 1603, 1616, 1643, 1649, 1658, 1706, 1710, 1757, 1770, 1789,
1811, 1840, 1877, 1879, 1881, 1898, 1924, 1981, 1985, 2010, 2034,
2038, 2040, 2042, 2051, 2060, 2066, 2072, 2106, 2136, 2147, 2151,
2176, 2198-2200, 2212, 2220-2224, 2230-2232, 2234-2238, 2240,
2245-2249, 2263, 2265, 2287, 2289, 2300, 2309, 2315, 2321, 2351,
2662, 2671, 2677, 2697, 2703, 2709, 2715, 2721, 2727, 2752, 2758,
2764, 2770, 2776, 2782, 2788, 2805, 2814, 2820, 2826, 2850, 2856,
2862, 2868, 2874, 2880, 2900, 2906, 2918, 2924, 2930, 2961, 2970,
2976, 2982, 2988, 2994, 3016, 3022, 3028, 3034, 3040, 3046, 3052,
3058, 3064, 3070, 3076, 3082, 3088, 3094, 3100, 3106, 3112, 3129,
3138, 3144, 3150, 3156, 3162, 3168, 3185, 3194, 3200, 3217, 3226,
3243, 3252, 3258, 3264, 3270, 3276, 3282, 3288, 3294, 3300, 3306,
3312, 3318, 3324, 3330, 3336, 3342, 3348, 3354, 3360, 3366, 3372,
3378, 3384, 3390, 3396, 3402, 3408, 3414, 3420, 3426, 3432, 3438,
3444, 3450, 3456, 3462, 3468, 3474, 3480, 3486, 3492, 3498, 3504,
3510, 3516, 3780, 3786, 3792 and 3856 can be produced in accordance
with the method of Example 26, Example 27 or Example 28.
A compound of Compound No. 2402 can be produced in accordance with
the method of Example 33.
Compounds of Compound No. 2418 and 2431 can be produced in
accordance with the method of Example 1, Example 6 or Example
22.
A compound of Compound No. 2478 can be produced in accordance with
the method of Example 35, Example 36, Example 37, Example 39 or
Example 40.
A compound of Compound No. 2492 can be produced in accordance with
the method of Example 41.
Compounds of Compound No. 1620, 1631, 2827 and 3001 can be produced
in accordance with the method of Example 635.
Compounds of Compound No. 1891, 1911, 1920, 1946, 1952, 1958, 3522,
3528, 3534, 3540, 3546, 35.52, 3558, 3570, 3576, 3582, 3588, 3594,
3600, 3606, 3612, 3618, 3624, 3636, 3642, 3648, 3654, 3660, 3666,
3672, 3678, 3684, 3690, 3696, 3702, 3708, 3714 and 3720 can be
produced in accordance with the method of Example 26, Example 27,
Example 28, Example 638, Example 639 or Example 640.
A compound of Compound No. 2327 can be produced in accordance with
the method of Example 636.
A compound of Compound No. 2733 can be produced in accordance with
the method of Example 637.
A compound of Compound No. 3811 can be produced in accordance with
the method of Example 645.
Compounds of Compound No. 3837 and 3849 can be produced in
accordance with the method of Example 646.
In the following Preparation example, all "%" mean % by weight.
PREPARATION EXAMPLE 1
Wettable Powder
A compound (10 parts by weight) of Example 1 (Compound No. 128),
Carplex #80D (available from Shionogi & Co. Ltd., 10 parts by
weight), GOHSENOL GL05 (available from The Nippon Synthetic
Chemical Industry Co., Ltd., 2 parts by weight), Newcol 291PG
(dioctylsulfosuccinate sodium salt, available from Nippon Nyukazai
Co., Ltd., 0.5 part by weight), Neogen Powder (available from
DAI-ICHI KOGYO SEIYAKU CO., LTD., 5 parts by weight), Radiolite
#200 (available from SHOWA CHEMICAL CO., LTD., 10 parts by weight)
and H Bifun (fine cray, available from Keiwa Rozai Co., Ltd, 62.5
parts by weight) were sufficiently mixed, and pulverized by
Ecksample Mill Type KII-1 (available from Fuji Paudal Co., Ltd.) to
obtain wettable powder.
PREPARATION EXAMPLE 2
Granule
A compound (5 parts by weight) of Example 61 (Compound No. 136),
sodium tripolyphosphate (available from Mitsui Chemicals, Inc., 2
parts by weight), Amycol No. 1 (dextrin, available from NIPPON
STARCH CHEMICAL CO., LTD., 1.5 parts by weight), bentonite
(available from Hojun Co., Ltd., 25 parts by weight) and Calfin 600
(calcium carbonate, available from Ashidachi Sekkai K.K., 66.5
parts by weight) were mixed in a kneader (available from Fujisangyo
Co., Ltd., Type FM-NW-5), and water (13 parts by weight) was added
to the mixture to carry out further mixing, and subjected to
extrusion granulation by using Dom Gran (available from Fuji Paudal
Co., Ltd., screen 1.0 mmo). The obtained granules were dried by
using a tray type dryer (available from Tabai K.K., PERFECT OVEN
Type PS-222, 60.degree. C.), and sieved to 600 to 1190 mm to obtain
granules.
PREPARATION EXAMPLE 3
Water Dispersible Granules
A compound (80 parts by weight) of Example 7 (Compound No. 140),
Geropon SC/213 (polycarboxylic acid type surfactant, available from
Rohdia K.K., 7 parts by weight), Neopelex No. 6F Powder
(dodecylbenzene sulfonate, KAO CORPORATION, 3 parts by weight),
Amycol No. 1 (5 parts by weight) and titanium oxide (SAKAI CHEMICAL
INDUSTRY CO., LTD., 5 parts by weight) are mixed, pulverized by air
mill (SK-JET O MIZER model 0101, available from SEISHIN ENTERPRISE
CO., LTD.,), then added to a rotary mixer, and granulated by
spraying water. When almost all the part become a size of 1.00 mm
to 0.15 mm, then the granules are taken out, and after drying in a
tray type dryer, they are sieved to obtain a granular wettable
powder with a size of 1.00 mm to 0.15 mm.
PREPARATION EXAMPLE 4
Suspension Consentrato
A compound (10 parts by weight) of Example 171 (Compound No. 506),
Newcol 291PG (1 parts by weight), Pearlrex CP (lignin sulfonic acid
calcium salt, available from NIPPON PAPER INDUSTRIES CO., LTD., 10
parts by weight), propylene glycol (available from Nippon Nyukazai
Co., Ltd., 10 parts by weight) and water (69 parts by weight) were
together mixed and pulverized in an attritor (MISUI MINING CO.,
LTD.) until the diameter of solid particles became 5 im or less. To
the pulverized slurry (90 parts by weight) was added 0.05% (W/W)
xanthane gum aqueous solution (10 parts by weight) and mixed to
obtain an aqueous suspension.
PREPARATION EXAMPLE 5
Wettable Powder
A compound (10 parts by weight) of Example 6 (Compound No. 139),
Compound A (10 parts by weight), Carplex #80D (available from
Shionogi & Co. Ltd., 10 parts by weight), GOHSENOL GL05-S
(available from The Nippon Synthetic Chemical Industry Co., Ltd., 2
parts by weight), Newcol 291PG (dioctylsulfosuccinate sodium salt,
available from Nippon Nyukazai Co., Ltd., 0.5 parts by weight),
Neogen Powder (available from DAI-ICHI KOGYO SEIYAKU CO., LTD., 5
parts by weight), Radiolite #200 (available from SHOWA CHEMICAL
CO., LTD., 10 parts by weight) and H Bifun (fine cray, available
from Keiwa Rozai Co., Ltd, 52.5 parts by weight) were sufficiently
mixed. The mixture was pulverized by air mill (SK-JET O MIZER Model
0101, available from SEISHIN ENTERPRISE CO., LTD.,) to obtain mixed
wettable powder of the compound (10%) of Example 6 and compound A
(10%).
PREPARATION EXAMPLE 6
Wettable Powder
A compound (10 parts by weight) of Example 23 (Compound No. 806),
Compound B (10 parts by weight), Carplex #80D (available from
Shionogi & Co. Ltd., 10 parts by weight), GOHSENOL GL05-S
(available from The Nippon Synthetic Chemical Industry Co., Ltd., 2
parts by weight), Newcol 291PG (dioctylsulfosuccinate sodium salt,
available from Nippon Nyukazai Co., Ltd., 0.5 parts by weight),
Neogen Powder (available from DAI-ICHI KOGYO SEIYAKU CO., LTD., 5
parts by weight), Radiolite #200 (available from SHOWA CHEMICAL
CO., LTD., 10 parts by weight) and H Bifun (fine cray, available
from Keiwa Rozai Co., Ltd, 52.5 parts by weight) were sufficiently
mixed. The mixture was pulverized by air mill (SK-JET O MIZER Model
0101, available from SEISHIN ENTERPRISE CO., LTD.,) to obtain a
mixed wettable powder of the compound (10%) of Example 23 and
Compound B (10%).
PREPARATION EXAMPLE 7
Granules
Compound A (61.22 parts by weight), Newcol 291PG (0.85 parts by
weight) and water (37.93 parts by weight) were mixed, and
pulverized by using an attritor (available from MISUI MINING CO.,
LTD.) until the average particle size became about 2 im to obtain a
slurry. To the slurry (98 parts by weight) was added Toxanone
(available from Sanyo Chemical Industries, Ltd., 2 parts by weight)
and then mixed to obtain Slurry 2. A compound (5 parts by weight)
of Example 171 (Compound No. 506), sodium tripolyphosphate
(available from Mitsui Chemicals, Inc., 2 parts by weight), Amycol
No. 1 (dextrin, available from NIPPON STARCH CHEMICAL CO., LTD.,
1.5 parts by weight), bentonite (available from Hojun Co., Ltd., 25
parts by weight) and Calfin 600 (calcium carbonate, available from
Ashidachi Sekkai K.K., 61.27 parts by weight) were mixed in a
kneader (available from Fujisangyo Co., Ltd., Type FM-NW-5), and
further Slurry 2 (8.33 parts by weight) were added and mixed. The
kneading material was subjected to extrusion granulation by using
Dom Gran (available from Fuji Paudal Co., Ltd., screen 1.0 mmo),
and the obtained granules were dried by using a tray type dryer
(available from Tabai K.K., PERFECT OVEN Type PS-222, 60.degree.
C.), then sieved to a size of 600 to 1190 mm to obtain granules of
the compound. (5%) of Example 171 and Ccompound A (5%).
PREPARATION EXAMPLE 8
Suspension Concentrato
A compound (11.11 parts by weight) of Example 1 (Compound No. 128),
Compound C (11.11 parts by weight), Newcol 291PG (1 parts by
weight), ligninsulfonic acid calcium salt (Pearlrex CP, available
from NIPPON PAPER INDUSTRIES CO., LTD., 10 parts by weight),
propylene glycol (available from Nippon Nyukazai Co., Ltd., 10
parts by weight) and water (56.78 parts by weight) were mixed and
pulverized in an attritor (MISUI MINING CO., LTD.) until a diameter
of solid particles became 5 im or less to obtain a slurry. To the
slurry (90 parts) was added 0.05% xanthane gum aqueous solution (10
parts by weight) and mixed to obtain a mixed aqueous suspension of
the compound (10%) of Example 1 and Compound C (10%).
PREPARATION EXAMPLE 9
Wettable Powder
A compound (10 parts by weight) of Example 23 (Compound No. 806),
Compound D (2 parts by weight), Carplex #80D (available from
Shionogi & Co. Ltd., 10 parts by weight), GOHSENOL GL05-S
(available from The Nippon Synthetic Chemical Industry Co., Ltd., 2
parts by weight), Newcol 291PG (dioctylsulfosuccinate sodium salt,
available from Nippon Nyukazai Co., Ltd., 0.5 parts by weight),
Neogen Powder (available from DAI-ICHI KOGYO SEIYAKU CO., LTD., 5
parts by weight), Radiolite #200 (available from SHOWA CHEMICAL
CO., LTD., 10 parts by weight) and H Bifun (fine cray, available
from Keiwa Rozai Co., Ltd, 60.5 parts by weight) were sufficiently
mixed. The mixture was pulverized by air mill (SK-JET O MIZER Model
0101, available from SEISHIN ENTERPRISE CO., LTD.,) to obtain a
mixed wettable powder of the compound (10%) of Example 23 and
Compound D (2%).
PREPARATION EXAMPLE 10
Wettable Powder
A compound (10 parts by weight) of Example 23 (Compound No. 806),
Compound E (8 parts by weight), Carplex #80D (available from
Shionogi & Co. Ltd., 10 parts by weight), GOHSENOL GL05-S
(available from The Nippon Synthetic Chemical Industry Co., Ltd., 2
parts by weight), Newcol 291PG (dioctylsulfosuccinate sodium salt,
available from Nippon Nyukazai Co., Ltd., 0.5 parts by weight),
Neogen Powder (available from DAI-ICHI KOGYO SEIYAKU CO., LTD., 5
parts by weight), Radiolite #200 (available from SHOWA CHEMICAL
CO., LTD., 10 parts by weight) and H Bifun (fine cray, available
from Keiwa Rozai Co., Ltd, 54.5 parts by weight) were sufficiently
mixed. The mixture was pulverized by air mill (SK-JET O MIZER Model
0101, available from SEISHIN ENTERPRISE CO., LTD.,) to obtain a
mixed wettable powder of the compound (10%) of Example 23 and
Compound E (8%).
PREPARATION EXAMPLE 11
Wettable Powder
In the same manner as in Preparation example 10 except for using
Compound F in place of Compound E, a mixed wettable powder of the
compound (10%) of Example 23 and Compound F (8%) was obtained.
TEST EXAMPLE 1
Tests of Herbicidal Effects and Crop Injury Against Paddy-field
Rice
A paddy soil was filled in 1/10,000 are pot, and seeds of
barnyardgrass (Echinochloa oryzicola Vasing.), Scirpus joncoides
and annual broad-leaved weeds (Lindernia spp., Rotala indica) which
are awaken from dormancy were mixed at the surface layer of 1 cm.
Also, tuber of Cyperus serotinus which is germinated was planted,
and further seedlings of paddy-field rice at 2.2-leaf stage were
transplanted, and they were grown under the flooded condition in a
greenhouse. After 3 days from transplanting, a predetermined
chemical dosage of the wettable powder prepared in accordance with
Preparation example 1 was diluted in water, and the solution was
applied to the pot and herbicidal effects and crop injury against
transplanted paddy-field rice were judged after 25 days from the
treatment. Also, 3-(2-allylphenoxy)-6-chloro-4-methoxypyridazine
described in Chemical Pharmaceutical Bulletin, 1972, vol. 20, No.
10, pp. 2191-2203 was used as Comparative compound. The results are
shown in Table 2. Incidentally, herbicidal effects and crop injury
against transplanted paddy-field rice were judged by the following
judgment standard, and "-" in the table means no test was carried
out.
Judgment standard 0: Growth inhibition rate; 0 to 10% 1: Growth
inhibition rate; 11 to 30% 2: Growth inhibition rate; 31 to 50% 3:
Growth inhibition rate; 51 to 70% 5 4: Growth inhibition rate; 71
to 90% 5: Growth inhibition rate; 91 to 100%.
TABLE-US-00002 TABLE 2 Crop injury against Chemical Herbicidal
effects trans- dosage Barnyard Broad Scirpus Cyperus planted Test
compound (g/a) grass leaf joncoides serotinus rice Compound of
Example 1 25 5 5 5 5 0 (Compound No. 128) Compound of Example 1
12.5 4 5 5 5 0 (Compound No. 128) Compound of Example 6 20 3 5 5 5
0 (Compound No. 139) Compound of Example 6 10 2 5 5 5 0 (Compound
No. 139) Compound of Example 14 10 0 5 4 5 0 (Compound No. 515)
Compound of Example 15 10 1 5 -- 5 0 (Compound No. 516) Compound of
Example 16 20 1 5 5 5 0 (Compound No. 704) Compound of Example 16
10 0 5 5 5 0 (Compound No. 704) Compound of Example 18 25 1 5 4 5 2
(Compound No. 738) Compound of Example 18 12.5 0 5 3 5 1 (Compound
No. 738) Compound of Example 19 25 1 5 4 5 1 (Compound No. 760)
Compound of Example 19 12.5 0 5 4 5 1 (Compound No. 760) Compound
of Example 21 10 2 5 5 5 0 (Compound No. 801) Compound of Example
22 25 2 5 4 4 2 (Compound No. 805) Compound of Example 22 12.5 1 5
2 3 1 (Compound No. 805) Compound of Example 23 20 4 5 5 5 2
(Compound No. 806) Compound of Example 23 10 3 5 5 5 0 (Compound
No. 806) Compound of Example 26 20 4 5 5 5 0 (Compound No. 2081)
Compound of Example 26 10 4 5 5 5 0 (Compound No. 2081) Compound of
Example 27 20 4 5 5 5 0 (Compound No. 2225) Compound of Example 27
10 2 5 4 5 0 (Compound No. 2225) Compound of Example 34 20 2 4 4 5
0 (Compound No. 2411) Compound of Example 34 10 1 2 2 5 0 (Compound
No. 2411) Compound of Example 49 25 2 5 4 5 0 (Compound No. 124)
Compound of Example 49 12.5 1 3 3 5 0 (Compound No. 124) Compound
of Example 50 25 3 5 4 5 0 (Compound No. 125) Compound of Example
50 12.5 2 5 3 5 0 (Compound No. 125) Compound of Example 51 25 2 5
5 5 0 (Compound No. 126) Compound of Example 51 12.5 2 4 3 5 0
(Compound No. 126) Compound of Example 52 20 4 5 5 5 0 (Compound
No. 127) Compound of Example 52 10 3 5 5 5 0 (Compound No. 127)
Compound of Example 55 25 2 5 4 5 0 (Compound No. 130) Compound of
Example 55 12.5 2 5 3 5 0 (Compound No. 130) Compound of Example 56
25 0 5 3 4 0 (Compound No. 131) Compound of Example 56 12.5 0 4 2 4
0 (Compound No. 131) Compound of Example 57 25 2 5 4 5 0 (Compound
No. 132) Compound of Example 57 12.5 2 5 3 5 0 (Compound No. 132)
Compound of Example 61 25 2 5 5 5 0 (Compound No. 136) Compound of
Example 61 12.5 1 5 5 5 0 (Compound No. 136) Compound of Example 72
20 3 5 5 5 0 (Compound No. 217) Compound of Example 72 10 3 5 5 4 0
(Compound No. 217) Compound of Example 85 10 2 4 3 5 0 (Compound
No. 284) Compound of Example 88 25 0 5 5 5 0 (Compound No. 292)
Compound of Example 88 12.5 0 4 4 5 0 (Compound No. 292) Compound
of Example 121 25 3 5 4 5 0 (Compound No. 385) Compound of Example
121 12.5 2 5 3 5 0 (Compound No. 385) Compound of Example 122 20 0
5 5 5 0 (Compound No. 386) Compound of Example 122 10 0 5 4 5 0
(Compound No. 386) Compound of Example 123 20 1 5 4 5 0 (Compound
No. 387) Compound of Example 123 10 0 5 3 4 0 (Compound No. 387)
Compound of Example 125 20 2 5 4 5 0 (Compound No. 391) Compound of
Example 125 10 1 5 3 4 0 (Compound No. 391) Compound of Example 129
25 2 5 4 5 0 (Compound No. 401) Compound of Example 129 12.5 1 5 3
4 0 (Compound No. 401) Compound of Example 154 20 2 5 5 5 0
(Compound No. 437) Compound of Example 154 10 1 5 3 5 0 (Compound
No. 437) Compound of Example 166 20 1 5 5 5 0 (Compound No. 472)
Compound of Example 166 10 0 5 5 5 0 (Compound No. 472) Compound of
Example 171 20 4 5 5 5 0 (Compound No. 506) Compound of Example 171
10 3 5 5 5 0 (Compound No. 506) Compound of Example 172 20 5 5 5 5
0 (Compound No. 507) Compound of Example 172 10 5 5 5 4 0 (Compound
No. 507) Compound of Example 179 20 1 4 4 5 0 (Compound No. 521)
Compound of Example 179 10 0 4 3 5 0 (Compound No. 521) Compound of
Example 180 25 0 5 3 5 0 (Compound No. 527) Compound of Example 180
12.5 0 5 2 5 0 (Compound No. 527) Compound of Example 181 20 2 5 4
5 0 (Compound No. 528) Compound of Example 181 10 1 5 3 4 0
(Compound No. 528) Compound of Example 182 20 2 5 4 5 0 (Compound
No. 529) Compound of Example 183 20 2 5 5 5 0 (Compound No. 531)
Compound of Example 183 10 1 5 5 5 0 (Compound No. 531) Compound of
Example 184 20 0 5 4 5 0 (Compound No. 532) Compound of Example 185
5 1 3 2 3 0 (Compound No. 534) Compound of Example 189 10 3 5 5 5 3
(Compound No. 539) Compound of Example 189 5 2 5 4 5 0 (Compound
No. 539) Compound of Example 191 20 5 5 5 5 5 (Compound No. 541)
Compound of Example 191 10 4 5 5 5 2 (Compound No. 541) Compound of
Example 192 20 5 3 5 5 1 (Compound No. 544) Compound of Example 192
10 2 2 5 5 0 (Compound No. 544) Compound of Example 202 10 2 5 -- 4
0 (Compound No. 571) Compound of Example 203 25 2 5 5 5 0 (Compound
No. 614) Compound of Example 203 12.5 1 5 5 5 0 (Compound No. 614)
Compound of Example 204 25 2 5 5 5 0 (Compound No. 618) Compound of
Example 204 12.5 2 5 5 5 0 (Compound No. 618) Compound of Example
205 25 1 5 5 5 0 (Compound No. 621) Compound of Example 205 12.5 0
5 5 5 0 (Compound No. 621) Compound of Example 212 25 2 5 5 5 0
(Compound No. 640) Compound of Example 212 12.5 1 5 5 5 0 (Compound
No. 640) Compound of Example 216 20 4 5 5 5 2 (Compound No. 658)
Compound of Example 216 10 4 5 5 5 0 (Compound No. 658) Compound of
Example 217 20 4 5 5 5 0 (Compound No. 659) Compound of Example 217
10 2 5 5 5 0 (Compound No. 659) Compound of Example 218 20 1 5 5 5
0 (Compound No. 662) Compound of Example 218 10 0 5 5 5 0 (Compound
No. 662) Compound of Example 219 20 4 5 5 -- 0 (Compound No. 663)
Compound of Example 219 10 3 5 5 -- 0 (Compound No. 663) Compound
of Example 232 20 4 5 4 5 0 (Compound No. 711) Compound of Example
232 10 4 5 3 4 0 (Compound No. 711) Compound of Example 233 20 4 5
5 5 0 (Compound No. 712) Compound of Example 233 10 3 4 3 4 0
(Compound No. 712) Compound of Example 234 25 0 5 4 5 0 (Compound
No. 716) Compound of Example 234 12.5 0 5 3 5 0 (Compound No. 716)
Compound of Example 235 20 3 5 5 5 0 (Compound No. 717) Compound of
Example 235 10 3 5 5 5 0 (Compound No. 717) Compound of Example 236
20 4 5 5 5 0 (Compound No. 719) Compound of Example 236 10 3 5 5 5
0 (Compound No. 719) Compound of Example 239 20 0 5 5 4 0 (Compound
No. 732) Compound of Example 240 25 3 5 4 5 0 (Compound No. 733)
Compound of Example 240 12.5 2 5 3 5 0 (Compound No. 733) Compound
of Example 241 20 3 5 4 5 0 (Compound No. 735) Compound of Example
241 10 1 5 3 5 0 (Compound No. 735) Compound of Example 242 25 4 5
4 5 0 (Compound No. 736) Compound of Example 242 12.5 3 5 3 5 0
(Compound No. 736) Compound of Example 243 25 2 5 4 5 0 (Compound
No. 737) Compound of Example 243 12.5 1 5 4 5 0 (Compound No. 737)
Compound of Example 245 20 4 5 5 5 0 (Compound No. 740) Compound of
Example 245 10 4 5 5 5 0 (Compound No. 740) Compound of Example 248
10 3 5 -- 5 0 (Compound No. 756) Compound of Example 248 5 1 5 -- 5
0 (Compound No. 756) Compound of Example 249 20 3 5 5 5 3 (Compound
No. 758) Compound of Example 249 10 2 5 5 5 0
(Compound No. 758) Compound of Example 250 20 4 5 5 5 0 (Compound
No. 759) Compound of Example 250 10 3 5 5 5 0 (Compound No. 759)
Compound of Example 253 20 4 5 5 5 5 (Compound No. 762) Compound of
Example 253 10 3 5 5 5 5 (Compound No. 762) Compound of Example 255
20 5 5 4 5 2 (Compound No. 778) Compound of Example 255 10 5 5 4 5
0 (Compound No. 778) Compound of Example 256 20 4 5 5 5 3 (Compound
No. 780) Compound of Example 256 10 3 5 5 5 2 (Compound No. 780)
Compound of Example 258 10 3 5 -- -- 0 (Compound No. 782) Compound
of Example 260 20 3 5 5 5 0 (Compound No. 802) Compound of Example
260 10 2 5 5 5 0 (Compound No. 802) Compound of Example 261 20 2 5
5 5 0 (Compound No. 803) Compound of Example 261 10 2 5 4 5 0
(Compound No. 803) Compound of Example 267 20 2 5 5 5 0 (Compound
No. 845) Compound of Example 267 10 1 5 4 5 0 (Compound No. 845)
Compound of Example 268 25 1 5 5 5 1 (Compound No. 846) Compound of
Example 268 12.5 0 5 5 5 1 (Compound No. 846) Compound of Example
269 20 3 5 5 5 5 (Compound No. 850) Compound of Example 269 10 2 5
5 5 3 (Compound No. 850) Compound of Example 271 25 2 5 4 4 1
(Compound No. 894) Compound of Example 271 12.5 1 5 2 3 0 (Compound
No. 894) Compound of Example 272 20 0 5 5 4 0 (Compound No. 896)
Compound of Example 272 10 0 5 4 4 0 (Compound No. 896) Compound of
Example 274 20 3 5 4 4 0 (Compound No. 914) Compound of Example 274
10 3 5 3 4 0 (Compound No. 914) Compound of Example 275 20 4 5 5 5
3 (Compound No. 931) Compound of Example 275 10 4 5 5 5 1 (Compound
No. 931) Compound of Example 276 20 4 5 4 5 0 (Compound No. 964)
Compound of Example 276 10 3 5 3 5 0 (Compound No. 964) Compound of
Example 277 20 1 5 5 5 0 (Compound No. 965) Compound of Example 277
10 0 5 -- 5 0 (Compound No. 965) Compound of Example 281 25 0 5 3 5
0 (Compound No. 998) Compound of Example 281 12.5 0 5 2 5 0
(Compound No. 998) Compound of Example 282 25 0 5 4 5 0 (Compound
No. 1000) Compound of Example 282 12.5 0 5 3 4 0 (Compound No.
1000) Compound of Example 285 20 0 5 5 3 0 (Compound No. 1013)
Compound of Example 285 10 0 5 4 2 0 (Compound No. 1013) Compound
of Example 286 25 0 5 5 5 0 (Compound No. 1016) Compound of Example
286 12.5 0 5 5 5 0 (Compound No. 1016) Compound of Example 287 25 0
5 5 3 0 (Compound No. 1020) Compound of Example 287 12.5 0 5 5 1 0
(Compound No. 1020) Compound of Example 288 20 1 5 5 5 0 (Compound
No. 1023) Compound of Example 288 10 0 5 5 5 0 (Compound No. 1023)
Compound of Example 289 25 0 5 5 5 0 (Compound No. 1027) Compound
of Example 289 12.5 0 4 4 4 0 (Compound No. 1027) Compound of
Example 290 10 0 5 4 5 0 (Compound No. 1040) Compound of Example
294 20 2 5 5 5 0 (Compound No. 1058) Compound of Example 294 10 1 5
5 5 0 (Compound No. 1058) Compound of Example 295 25 1 5 5 5 0
(Compound No. 1060) Compound of Example 295 12.5 0 5 5 5 0
(Compound No. 1060) Compound of Example 296 20 2 5 5 5 0 (Compound
No. 1061) Compound of Example 296 10 1 5 5 5 0 (Compound No. 1061)
Compound of Example 303 25 1 4 4 5 0 (Compound No. 1083) Compound
of Example 303 12.5 0 3 3 5 0 (Compound No. 1083) Compound of
Example 304 20 4 5 5 5 0 (Compound No. 1086) Compound of Example
304 10 4 5 4 4 0 (Compound No. 1086) Compound of Example 305 10 1 5
5 5 0 (Compound No. 1088) Compound of Example 306 10 1 5 5 5 0
(Compound No. 1089) Compound of Example 307 20 4 5 5 5 0 (Compound
No. 1091) Compound of Example 307 10 3 5 5 5 0 (Compound No. 1091)
Compound of Example 308 20 4 5 5 5 0 (Compound No. 1096) Compound
of Example 308 10 2 5 4 5 0 (Compound No. 1096) Compound of Example
309 20 5 5 5 5 5 (Compound No. 1099) Compound of Example 309 10 4 5
5 5 2 (Compound No. 1099) Compound of Example 310 20 5 5 5 5 0
(Compound No. 1100) Compound of Example 310 10 4 5 5 5 0 (Compound
No. 1100) Compound of Example 311 20 3 5 5 5 0 (Compound No. 1102)
Compound of Example 311 10 1 5 4 4 0 (Compound No. 1102) Compound
of Example 313 20 1 5 -- -- 0 (Compound No. 1115) Compound of
Example 315 20 4 5 -- 5 0 (Compound No. 1119) Compound of Example
316 20 3 5 -- -- 0 (Compound No. 1120) Compound of Example 316 10 2
5 -- -- 0 (Compound No. 1120) Compound of Example 317 25 0 5 3 5 1
(Compound No. 1122) Compound of Example 317 12.5 0 4 2 5 0
(Compound No. 1122) Compound of Example 318 20 1 5 5 5 0 (Compound
No. 1123) Compound of Example 318 10 0 5 5 5 0 (Compound No. 1123)
Compound of Example 319 20 3 5 5 5 0 (Compound No. 1124) Compound
of Example 319 10 2 5 5 5 0 (Compound No. 1124) Compound of Example
320 25 2 5 5 5 0 (Compound No. 1125) Compound of Example 320 12.5 1
5 5 5 0 (Compound No. 1125) Compound of Example 323 20 4 5 5 5 0
(Compound No. 1140) Compound of Example 323 10 3 5 5 5 0 (Compound
No. 1140) Compound of Example 327 20 4 5 5 5 0 (Compound No. 1266)
Compound of Example 327 10 4 5 5 5 0 (Compound No. 1266) Compound
of Example 328 20 4 5 5 5 0 (Compound No. 1387) Compound of Example
328 10 3 3 3 5 0 (Compound No. 1387) Compound of Example 329 20 4 5
5 5 0 (Compound No. 1391) Compound of Example 329 10 2 5 5 5 0
(Compound No. 1391) Compound of Example 345 20 4 5 5 5 0 (Compound
No. 1658) Compound of Example 345 10 3 5 5 5 0 (Compound No. 1658)
Compound of Example 347 20 4 5 5 5 0 (Compound No. 1710) Compound
of Example 347 10 3 5 5 5 0 (Compound No. 1710) Compound of Example
349 20 4 5 5 5 0 (Compound No. 1789) Compound of Example 349 10 3 4
4 5 0 (Compound No. 1789) Compound of Example 352 20 4 5 5 -- 0
(Compound No. 1879) Compound of Example 356 20 3 5 5 5 0 (Compound
No. 1981) Compound of Example 356 10 2 4 3 5 0 (Compound No. 1981)
Compound of Example 357 20 3 5 5 5 0 (Compound No. 1985) Compound
of Example 357 10 2 5 5 5 0 (Compound No. 1985) Compound of Example
359 20 5 5 4 5 0 (Compound No. 2038) Compound of Example 359 10 4 3
3 5 0 (Compound No. 2038) Compound of Example 360 20 4 5 5 5 0
(Compound No. 2040) Compound of Example 360 10 3 5 5 5 0 (Compound
No. 2040) Compound of Example 361 20 3 5 5 5 0 (Compound No. 2042)
Compound of Example 361 10 2 5 5 4 0 (Compound No. 2042) Compound
of Example 365 20 3 5 5 5 0 (Compound No. 2151) Compound of Example
365 10 2 5 4 5 0 (Compound No. 2151) Compound of Example 394 20 3 5
5 5 0 (Compound No. 2289) Compound of Example 394 10 2 5 4 5 0
(Compound No. 2289) Comparative compound 25 0 1 0 0 0
TEST EXAMPLE 2
Tests of Herbicidal Effects (Soil Treatment)
Upland soll was filled in 150 cm.sup.2 pot, and seeds of
barnyardgrass and indian mustard (Brassica juncea (L.) Czern. et
Coss) were sowed, and grown in a greenhouse. At the next day of
seeding, a predetermined chemical dosage of the wettable powder
prepared in accordance with Preparation example 1 was diluted in
water and applied to soil surface. After 21 days from the
treatment, herbicidal effects were judged in accordance with the
judgment standard of Test example 1, and the results were shown in
Table 3.
TABLE-US-00003 TABLE 3 Test of herbicidal effects Herbicidal
effects Dosage Barnyard- indian Test compound (kg/a) grass mustard
Example 23 2 4 5 (Compound No. 806) Example 171 5 5 5 (Compound No.
506) Example 236 5 3 5 (Compound No. 719) Example 245 5 3 5
(Compound No. 740) Example 249 5 4 5 (Compound No. 758) Example 256
5 3 5 (Compound No. 780) Example 309 5 5 5 (Compound No. 1099)
Example 310 5 5 5 (Compound No. 1100)
TEST EXAMPLE 3
Test of Herbicidal Effects (Foliar Treatment)
Upland soil was filled in 150 cm.sup.2 pot, and seeds of
velvetleaf, tall morningglory, indian mustard, black nightshade
redroot pigweed were sowed, and grown in a greenhouse. After the
weeds were grown with 10 to 15 cm or so, a predetermined chemical
dosage of the wettable powder prepared in accordance with
Preparation example 1 was diluted with water containing 0.05% of
GRAMIN-S and applied as a foliar treatment. After 14 days from the
treatment, herbicidal effects were judged in accordance with the
judgment standard of Test example 1, and the results were shown in
Table 4. Incidentally, "-" in the table means no test was carried
out.
TABLE-US-00004 TABLE 4 Test of herbicidal effects Herbicidal
effects Chemical Tall dosage Velvet- Morning Indian Black Redroot
Test compound (kg/a) leaf glory mustard Nightshade pigweed Example
23 2 4 5 5 5 4 (Compound No. 806) Example 236 0.5 -- 4 3 -- 3
(Compound No. 719)
TEST EXAMPLE 4
Tests of Herbicidal Effects and Crop Injury Against Transplanted
Paddy-field Rice
Paddy filed soil was filled in 1/5000 are Wagner pot, seeds of
barnyardgrass (Echinochloa oryzicola Vasing.), Scirpus joncoides
and annual broad-leaved weeds (Lindernia spp. and Rotala indica)
which are awaken from dormancy were mixed at the surface layer of 1
cm. Also, tubers of Cyperus serotinus, Sagittaria pygmaea and
Eleocharis kuroguwai which are awaken from dormancy were planted,
and further seedlings of paddy-field ric at 2.2-leaf stage were
transplantedand they were grown under the flooded condition in a
greenhouse. After 3 days from the transplanting, a predetermined
chemical dosage of the wettable powder prepared in accordance with
Preparation example 5 was diluted with water, and applied to the
pot. After 25 days, herbicidal effects and crop injury against
transplanted paddy-field rice were judged according to the
following judgment standard, and the results were shown in Table 5.
Incidentally, "-" in the table means a composition containing no
effective ingredient.
Judgment standard 0: Growth inhibition rate; 0 to 15% 1: Growth
inhibition rate; 16 to 35% 2: Growth inhibition rate; 36 to 55% 3:
Growth inhibition rate; 56 to 75% 4: Growth inhibition rate; 76 to
95% 5: Growth inhibition rate; 96 to 100%.
TABLE-US-00005 TABLE 5 Tests of herbicidal effects and crop injury
against transplanted paddy-field rice Second herbi- cidally
3-phenoxy-4- active Crop injury pyridazinol com- Herbicidal effects
against Test derivatives pound Barnyard Broad Scirpus Sagittaria
Cyperus Eleochari- s transplanted No. (g/a) (g/a) grass leaf
joncoides pygmaea serotinus kuroguwai rice 1 Example 1 (10) A(5) 5
5 5 5 5 5 0 2 Example 1 (5) A(5) 5 5 5 5 5 4 0 3 Example 1 (10)
B(5) 5 5 5 5 5 4 0 4 Example 1 (5) B(5) 5 5 5 5 5 4 0 5 Example 1
(10) C(5) 5 5 5 5 5 4 0 6 Example 1 (5) C(5) 5 5 5 5 5 4 0 7
Example 1 (10) -- 4 4 4 4 5 0 0 8 Example 1 (5) -- 2 3 2 4 4 0 0 9
Example 6 (10) A(5) 5 5 5 5 5 5 0 10 Example 6 (5) A(5) 5 5 5 5 5 5
0 11 Example 6 (10) C(5) 5 5 5 5 5 5 0 12 Example 6 (5) C(5) 5 5 5
5 5 5 0 13 Example 6 (10) -- 2 5 5 5 5 3 0 14 Example 6 (5) -- 1 5
5 5 5 2 0 15 Example 16 A(5) 5 5 5 5 5 2 0 (10) 16 Example 16 (5)
A(5) 5 5 5 5 5 2 0 17 Example 16 B(5) 5 5 5 5 5 3 0 (10) 18 Example
16 (5) B(5) 5 5 5 5 5 2 0 19 Example 16 -- 0 5 5 4 5 1 0 (10) 20
Example 16 (5) -- 0 5 3 3 4 0 0 21 Example 23 A(5) 5 5 5 5 5 5 0
(10) 22 Example 23 (5) A(5) 5 5 5 5 5 3 0 23 Example 23 B(5) 5 5 5
5 5 5 0 (10) 24 Example 23 (5) B(5) 5 5 5 5 5 3 0 25 Example 23
C(5) 5 5 5 5 5 5 0 (10) 26 Example 23 (5) C(5) 5 5 5 5 5 2 0 27
Example 23 -- 3 5 5 5 5 3 0 (10) 28 Example 23 (5) -- 2 5 5 5 5 2 0
29 Example 47 A(5) 5 5 5 5 5 5 0 (10) 30 Example 47 (5) A(5) 5 5 5
5 5 5 0 31 Example 47 -- 3 5 5 5 5 2 0 (10) 32 Example 47 (5) -- 3
5 4 5 5 1 0 33 Example 171 A(5) 5 5 5 5 5 4 0 (10) 34 Example 171
A(5) 5 5 5 5 5 4 0 (5) 35 Example 171 B(5) 5 5 5 5 5 4 0 (10) 36
Example 171 B(5) 5 5 5 5 5 4 0 (5) 37 Example 171 C(5) 5 5 5 5 5 4
0 (10) 38 Example 171 C(5) 5 5 5 5 5 3 0 (5) 39 Example 171 -- 3 5
5 5 5 3 0 (10) 40 Example 171 -- 2 5 5 5 5 2 0 (5) 41 Example 191
A(5) 5 5 5 5 5 3 0 (2.5) 42 Example 191 B(5) 5 5 5 5 5 3 0 (2.5) 43
Example 191 C(5) 5 5 5 5 5 3 0 (2.5) 44 Example 191 -- 1 3 3 2 5 1
0 (2.5) 45 Example 245 A(5) 5 5 5 5 5 3 0 (10) 46 Example 245 A(5)
5 5 5 5 5 2 0 (5) 47 Example 245 C(5) 5 5 5 5 5 3 0 (10) 48 Example
245 C(5) 5 5 5 5 5 2 0 (5) 49 Example 245 -- 4 5 5 5 5 1 0 (10) 50
Example 245 -- 3 5 5 4 4 0 0 (5) 51 Example 249 A(5) 5 5 5 5 5 3 0
(10) 52 Example 249 A(5) 5 5 5 5 5 3 0 (5) 53 Example 249 -- 2 5 5
5 5 2 0 (10) 54 Example 249 -- 1 5 3 5 5 1 0 (5) 55 Example 288
A(5) 5 5 5 5 5 5 0 (10) 56 Example 288 A(5) 5 5 5 5 5 5 0 (5) 57
Example 288 -- 0 5 5 5 5 3 0 (10) 58 Example 288 -- 0 5 5 5 4 2 0
(5) 59 -- A 5 5 4 5 4 2 0 (30) 60 -- A(5) 3 4 3 4 2 0 0 61 -- B 5 5
4 5 4 2 0 (30) 62 -- B(5) 3 4 3 4 2 0 0 63 -- C 5 5 4 5 4 2 0 (30)
64 -- C(5) 3 5 2 4 1 0 0
TEST EXAMPLE 5
Tests of Herbicidal Effects and Crop Injury Against Upland Crops
(Soil Treatment)
Upland soil was filled in 150 cm.sup.2 pot, and seeds of
barnyardgrass, Cyperus esculentus L., velvetleaf, black nightshade,
tall morningglory and corn were sowed, and grown in a greenhouse.
At the next day of seeding, a predetermined chemical dosage of the
wettable powder prepared in accordance with Preparation example 5
was diluted with water and applied to soil surface. After 21 days
from the treatment, herbicidal effects and crop injury against corn
were judged according to the following judgment standard, and the
results were shown in Tables 6 to 8. Incidentally, "-" in the table
means that the composition does not contain the effective
ingredient.
Judgment standard 0: Growth inhibition rate; 0 to 9% 1: Growth
inhibition rate; 10 to 19% 2: Growth inhibition rate; 20 to 29% 3:
Growth inhibition rate; 30 to 39% 4: Growth inhibition rate; 40 to
49% 5: Growth inhibition rate; 50 to 59% 6: Growth inhibition rate;
60 to 69% 7: Growth inhibition rate; 70 to 79% 8: Growth inhibition
rate; 80 to 89% 9: Growth inhibition rate; 90 to 98% 10: Growth
inhibition rate; 99 to 100%.
TABLE-US-00006 TABLE 6 Tests of herbicidal effects and crop injury
against corn (Example 23 + compound D) Second 3-phenoxy-
herbicidally Crop 4-pyridazinol active Herbicidal effects injury
Test derivatives compound Barnyard- Tall Black against No. (g/ha)
(g/ha) grass Velvetleaf Morningglory Nightshade corn 1 Example 23
D(25) 10 10 9 10 0 (250) 2 Example 23 D(25) 10 10 7 10 0 (125) 3
Example 23 D(25) 10 10 8 10 0 (63) 4 -- D(25) 10 9 5 9 0 5 Example
23 D(12.5) 10 10 9 10 0 (250) 6 Example 23 D(12.5) 10 10 5 9 0
(125) 7 Example 23 D(12.5) 10 9 3 9 0 (63) 8 -- D(12.5) 10 7 0 9 0
9 Example 23 D(6.3) 10 10 6 9 0 (250) 10 Example 23 D(6.3) 9 10 5
10 0 (125) 11 Example 23 D(6.3) 5 9 1 9 0 (63) 12 -- D(6.3) 3 6 2 5
0
TABLE-US-00007 TABLE 7 Test of herbicidal effects and chemical
damage against corn (Example 23 + compound E) 3-phenoxy- Second
4-pyrida- herbi- zinol cidally crop deriva- active Herbicidal
effects injury Test tives compound Barnyard- Cyperus Velvet-
TallMorning Black against No. (g/ha) (g/ha) grass esculentus leaf
glory Nightshade corn 1 Example 23 E(200) 10 9 10 10 10 0 (125) 2
Example 23 E(200) 10 9 10 10 10 0 (63) 3 -- E(200) 10 8 10 10 9 0 4
Example 23 E(100) 10 9 10 10 10 0 (125) 5 Example 23 E(100) 10 8 10
10 9 0 (63) 6 -- E(100) 9 8 7 7 6 0 7 Example 23 E(50) 9 8 10 8 10
0 (125) 8 Example 23 E(50) 10 9 9 7 9 0 (63) 9 -- E(50) 7 8 7 6 7
0
TABLE-US-00008 TABLE 8 Test of herbicidal effects and chemical
damage against corn (Example 23 + compound F) 3- phenoxy- 4- Second
pyrida- herbi- zinol cidally Crop deriva- active Herbicidal effects
injury Test tives compound Barnyard- Cyperus Tall Black against No.
(g/ha) (g/ha) grass esculentus Velvetleaf Morningglory Nightshade
corn- 1 Example F(100) 10 9 10 9 10 0 23 (125) 2 Example F(100) 10
9 10 9 10 0 23 (63) 3 -- F(100) 9 9 10 8 8 0 4 Example F(50) 10 9
10 7 10 0 23 (125) 5 Example F(50) 9 9 10 7 10 0 23 (63) 6 -- F(50)
8 9 10 5 3 0 7 Example F(25) 9 9 10 7 9 0 23 (125) 8 Example F(25)
7 8 9 5 10 0 23 (63) 9 -- F(25) 4 8 9 2 6 0
TEST EXAMPLE 6
Tests of Herbicidal Effects and Crop Injury Against Upland crops
(foliar treatment)
Upland soil was filled in 150 cm.sup.2 pot, and seeds of
barnyardgrass, Cyperus esculentus L., velvetleaf, black nightshade,
tall morningglory and corn were sowed, and grown in a greenhouse.
After the weeds were grown with 10 to 15 cm or so, a predetermined
chemical dosage of the wettable powder prepared in accordance with
Preparation example 5 was diluted with water containing 0.05% of
GRAMIN S and applied as a foliar treatment. After 14 days from the
treatment, herbicidal effects and crop injury were judged in
accordance with the judgment standard of Test example 5, and the
results were shown in Tables 9 and 10. Incedentally, "-" in the
table means no effective ingredient was contained.
TABLE-US-00009 TABLE 9 Test of herbicidal effects and crop injury
against corn (Example 23 + compound E) 3-phenoxy- Second 4-pyrida-
herbi- zinol cidally crop deriva- active Herbicidal effects injury
Test tives compound Barnyard Cyperus Velvet- TallMorning Black
against No. (g/ha) (g/ha) grass esculentus leaf glory Nightshade
corn 1 Example 23 E(200) 9 8 10 9 10 0 (250) 2 Example 23 E(200) 9
9 10 9 10 0 (125) 3 Example 23 E(200) 9 9 10 8 10 0 (63) 4 --
E(200) 7 8 10 9 10 0 5 Example 23 E(100) 9 9 10 9 10 0 (250) 6
Example 23 E(100) 9 8 10 9 10 0 (125) 7 Example 23 E(100) 8 9 10 8
9 0 (63) 8 -- E(100) 2 7 10 7 10 0 9 Example 23 E(50) 8 9 10 7 10 0
(250) 10 Example 23 E(50) 5 8 10 9 10 0 (125) 11 Example 23 E(50) 2
8 10 8 10 0 (63) 12 -- E(50) 1 6 9 6 9 0
TABLE-US-00010 TABLE 10 Test of herbicidal effects and crop injury
against corn (Example 23 + compound F) Second herbi- 3-phenoxy-4-
cidally Crop pyridazinol active Herbicidal effects injury Test
derivatives compound Barnyard- Cyperus Velvet- TallMorning Black
agai- nst No. (g/ha) (g/ha) grass esculentus leaf glory Nightshade
corn 1 Example 23 F(100) 8 7 10 9 10 0 (250) 2 Example 23 F(100) 6
7 9 9 10 0 (125) 3 -- F(100) 2 6 10 9 9 0 4 Example 23 F(50) 4 7 10
9 10 0 (250) 5 Example 23 F(50) 2 7 10 9 10 0 (125) 6 -- F(50) 0 5
10 5 10 0 7 Example 23 F(25) 1 7 10 6 10 0 (250) 8 Example 23 F(25)
1 6 10 5 10 0 (125) 9 -- F(25) 0 4 9 2 7 0
Utilizability in Industry
The compounds of the present invention have herbicidal activities,
and can be used as a herbicidal composition for a paddy field,
upland field, orchard, pasture, turf, forest or non-crop land.
The compounds of the present invention show herbicidal activities
against various weeds which cause problems in a paddy field, for
example, annual broad-leaved weeds such as Lindernia spp.,
Vandellia angustifolia Benth., Rotala indica, Elatine triandra,
Monochoria vaginaris, Murdannia keisak, Dopatirum junceum (Roxb.)
Hamilt, Ammannia multiflora, etc.; perennial arrowhead weeds such
as Sagittaria pygmaea Miq., arrowhead (Sagittaria trifolia L.),
Alisma canaliculatum, etc.; annual Cyperaceous weeds such as
flatsedge, smallflower umbrellasedge, etc.; perennial Cyperaceous
weeds such as needle spikerush, Scirpus joncoides, Cyperus
serotinus, Scrips Nipponicus Makino, etc.; or annual perennial
Graminaceous weeds such as barnyardgrass, Leersia oryzoides (L.)
Swartz., and the like, and show no crop injury against rice which
causes any problem.
Also, the compounds of the present invention show herbicidal
activities both by foliar application and soil application agaist
valious kinds of weeds, which are troublesome in upland fields.
Moreover, they can be used not only in a paddy field and an upland
filed, but also in an orchard, a mulberry field and a non-crop
land.
Also, weeding spectrum of the herbicidal composition of the present
invention can be enlarged by using 3-phenoxy-4-pyridazinol
derivatives and a second herbicidally active compound in admixture
which are effective ingredients than its range to be applied which
had been obtained with a single agent use. The weeding spectrum of
the composition according to the present invention covers
Graminaceous weeds, annual broad-leaved weeds and whole perennial
weeds such as Arrowhead, Cyperaceous weeds, etc. Moreover, the
composition of the present invention has high safety to paddy-field
rice or upland crops, and has a wide application window. Also, the
composition of the present invention shows synergistic effects in
the herbicidal effects, and shows sufficient effects with a mixture
of compounds with a markedly lower chemical dosage than the
chemical dosage is used as a single agent in the case where each.
As a result, the composition of the present invention is hightened
in herbicidal activity so that it is sufficient with a one time
treatment agent, and its effects are continued for a long period of
time. Also, the composition of the present invention shows no crop
injury against paddy-field rice, and it can be applied both of
before transplanting and immediately after transplanting.
* * * * *